Antibiotics 11 01079 v2

antibiotics
Review
Antibiotic Resistance in Bacteria—A Review
Renata Urban-Chmiel 1, * , Agnieszka Marek 1 , Dagmara St˛epień-Pyśniak 1 , Kinga Wieczorek 2 ,
Marta Dec 1 , Anna Nowaczek 1 and Jacek Osek 2
1 Department of Veterinary Prevention and Avian Diseases, Faculty of Veterinary Medicine, University of Life
Sciences in Lublin, 20-033 Lublin, Poland
2 Department of Hygiene of Food of Animal Origin, National Veterinary Research Institute, Partyzantów 57,
24-100 Puławy, Poland
* Correspondence: renata.urban@up.lublin.pl
Abstract: Background: A global problem of multi-drug resistance (MDR) among bacteria is the
cause of hundreds of thousands of deaths every year. In response to the significant increase of MDR
bacteria, legislative measures have widely been taken to limit or eliminate the use of antibiotics,
including in the form of feed additives for livestock, but also in metaphylaxis and its treatment,
which was the subject of EU Regulation in 2019/6. Numerous studies have documented that bacteria
use both phenotypis and gentic strategies enabling a natural defence against antibiotics and the
induction of mechanisms in increasing resistance to the used antibacterial chemicals. The mechanisms
presented in this review developed by the bacteria have a significant impact on reducing the ability
to combat bacterial infections in humans and animals. Moreover, the high prevalence of multi-
resistant strains in the environment and the ease of transmission of drug-resistance genes between
the different bacterial species including commensal flora and pathogenic like foodborne pathogens
(E. coli, Campylobacter spp., Enterococcus spp., Salmonella spp., Listeria spp., Staphylococcus spp.) favor
the rapid spread of multi-resistance among bacteria in humans and animals. Given the global
threat posed by the widespread phenomenon of multi-drug resistance among bacteria which are
Citation: Urban-Chmiel, R.; Marek,
dangerous for humans and animals, the subject of this study is the presentation of the mechanisms
A.; St˛epień-Pyśniak, D.; Wieczorek, of resistance in most frequent bacteria called as “foodborne pathoges” isolated from human and
K.; Dec, M.; Nowaczek, A.; Osek, J. animals. In order to present the significance of the global problem related to multi-drug resistance
Antibiotic Resistance in Bacteria—A among selected pathogens, especially those danger to humans, the publication also presents statistical
Review. Antibiotics 2022, 11, 1079. data on the percentage range of occurrence of drug resistance among selected bacteria in various
https://doi.org/10.3390/ regions of the world. In addition to the phenotypic characteristics of pathogen resistance, this review
antibiotics11081079 also presents detailed information on the detection of drug resistance genes for specific groups of
Academic Editor: Marc Maresca antibiotics. It should be emphasized that the manuscript also presents the results of own research
i.e., Campylobacter spp., E. coli or Enetrococcus spp. This subject and the presentation of data on the
Received: 4 July 2022
risks of drug resistance among bacteria will contribute to initiating research in implementing the
Accepted: 6 August 2022
prevention of drug resistance and the development of alternatives for antimicrobials methods of
Published: 9 August 2022
controlling bacteria.
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in Keywords: antibiotic resistance; bacteria; resistance genes; antimicrobials
published maps and institutional affil-
iations.
1. Introduction
Copyright: © 2022 by the authors.
Widespread resistance to antibiotics among bacteria is the cause of hundreds of thou-
Licensee MDPI, Basel, Switzerland. sands of deaths every year. The most serious problem is the constantly growing number of
This article is an open access article bacteria resistant to commonly used antibiotics, including drugs of last resort (vancomycin).
distributed under the terms and The speed with which resistance genes can spread around the world confirms the worrying
conditions of the Creative Commons rise in a problem that affects public health on a global scale and requires international coop-
Attribution (CC BY) license (https:// eration (Supplementary Table S1) In response to the significant increase in the population
creativecommons.org/licenses/by/ of multi-drug resistant strains observed worldwide, in 2014 the World Health Organization
4.0/). (WHO) recognized this phenomenon as a major global health threat [1].
Antibiotics 2022, 11, 1079. https://doi.org/10.3390/antibiotics11081079 https://www.mdpi.com/journal/antibiotics

Antibiotics 2022, 11, 1079 2 of 40
Legislative measures have widely been taken to limit or eliminate the use of antibiotics,
including in the form of feed additives for livestock, but also as antibacterial agents in
metaphylaxis and treatment, which was the subject of EU Regulation 2019/6 [2].
As part of the strategies undertaken to reduce of drug resistance among microor-
ganisms, it is also necessary to increase the research potential in such areas as genetic
improvement of animals in order to identify markers associated with increased innate resis-
tance to pathogens, search for new antimicrobial agents, and determine the role of bacteria
in the transmission of antibiotic resistance to human and animal microbial flora. The cur-
rently implemented strategies for overcoming antibiotic resistance rely on the alternative
use of bacteriophages or their enzymes, the development of next-generation vaccines. Also
important is the use of new feeding-based regimes for animals with prebiotics, probiotics,
bacterial subproducts, and phytobiotics [3]. There is also great interest in proteins and
peptides with bactericidal activity synthesized by bacteria, plants, invertebrates, vertebrates
and mammals. This solution is based on the use of antimicrobial peptides produced by gen-
erally recognized as safe (GRAS) bacteria like Lactobacillus spp., Streptomyces, Micrococcus
or yeast Saccharomyces and Candidia [4].
The fight against the development of antibiotic resistance has conventionally taken
place mainly in clinical conditions, and more recently in agriculture as well, with the aim of
limiting transmission of resistant bacteria and preventing their selection during treatment
with antibiotics. Recent years have seen an increasing understanding of the role of the
environment as an important source and pathway of the dissemination of drug resistance
among bacteria.
2. Mechanisms of Acquisition of Drug Resistance among Bacteria

The simplest type of resistance is a natural lack of susceptibility, called innate resis-
tance. This is a constant trait of a species, strain, or whole group of bacteria. A given
microorganism is insensitive to an antibiotic due to its ‘innate’ resistance to certain groups
of antibiotics. It may be linked to the absence of a receptor for the antibiotic, low affinity,
cell wall impermeability, or enzyme production [5].
Changes in the susceptibility of bacteria can be primary or secondary. Primary resis-
tance arises as a result of a spontaneous mutation and can appear without contact with a
drug. This type of resistance is encoded chromosomally and is not transmitted to other
bacterial species. The frequency of occurrence of mutated bacteria is low, but in the pres-
ence of an antibiotic, mutants have an advantage over the rest of the population, and thus
they survive and outnumber susceptible populations. They can spread to other ecological
niches in the same individual or can be transferred to other macroorganisms. While de-
fending themselves against antibacterial agents, including antibiotics, in the course of their
evolution, bacteria have developed a variety of mechanisms counteracting the effects of
antibacterial agents. As a result of the acquisition of resistance genes, bacteria become partly
or entirely resistant to a given antibiotic by developing various effector mechanisms [6].
Based on numerous scientific studies conducted from the mid-20th century, a number
of mechanisms explaining bacterial resistance to antibiotics have been proposed. Bacteria
are currently believed to acquire antibiotic resistance via active removal of the antibiotic
from the cell, enzymatic modifications of the antibiotic, modifications of cell components
which are the target of the antibiotic, overexpression of an enzyme inactivated by the
antibiotic, a change in the permeability of bacteria cell membranes, production of an
alternative metabolic pathway, an increase in the concentration of a metabolite which is an
antagonist of the antibiotic, a reduction in the amount or activity of an enzyme activating
the precursor of the antibiotic, modifications in regulatory systems not associated with the
direct mechanism of action of the antibiotic, or a reduction in the demand for the product
of the inhibited metabolic pathway [7,8].
Numerous studies have documented that bacteria use two main genetic strategies
enabling natural defence against antibiotics: gene mutation, often associated with the mech-
Antibiotics 2022, 11, 1079 3 of 40
anism of action of an antibacterial compound, and acquisition of foreign DNA encoding

determinants of resistance via horizontal gene transfer [9].
Horizontal gene transfer plays an important role in the spread of both known and
new, as yet unidentified resistance genes. This mechanism allows resistance to expand
beyond specific clones. In this way gene transfer makes resistance genes available for a
much larger number of bacteria, even breaking the species barrier between environmental
(non-pathogenic) bacteria and pathogens in a given living environment of microorgan-
isms [10]. The process of horizontal transfer of drug resistance genes between bacteria
can take place in any environment where they are present. However, for resistance genes
to be transferred horizontally from environmental to pathogenic bacteria, they must at
least temporarily be present in the same environment. In addition, horizontal gene trans-
fer is much more likely between bacteria that are closely phylogenetically related [11].
Finally, transfer of genetic material between bacterial cells is induced by stressors such
as antibiotics [12], and potentially also metals and biocides [13]. Selection of antibiotics
also contributes to the establishment of transferred resistance genes in a new host. There-
fore, transfer of resistance to pathogens can be expected to be relatively common between
bacteria associated with humans [14], especially during treatment with antibiotics. In
contrast, transfer of resistance genes to pathogens from environmental bacteria that occupy
a different habitat and are often less closely phylogenetically related would most likely
be less common, although environmental stressors can induce horizontal gene transfer to
and from (opportunistic) human pathogens in environmental conditions. This means that
when a resistance factor is transferred to a human pathogen, there is a greater chance of its
further spread between commensals and pathogens than of transfer to another pathogen
from environmental bacteria.
Mechanisms leading to secondary resistance, which develop in conditions of con-
tact between the microorganism and an antibacterial drug, are much more complex. The
secondary resistance mechanism is extrachromosomal. The genes responsible for this phe-
nomenon are located in small circular molecules of DNA called plasmids in the cytoplasm.
One plasmid may contain genes of resistance to several different antimicrobials. Plasmids
can transfer genes encoding resistance from one bacterial cell to another. Plasmids are
transferred mainly via conjugation and transduction. During conjugation, plasmids are
transferred by direct contact between two or more bacterial cells via strands of protein pro-
duced by them. Bacteria of different species and genera, often phylogenetically remote, can
take part in the conjugation process. Transfer of resistance from saprophytic to pathogenic
bacteria in this manner is particularly unfavourable. Transduction is the process of transfer
of plasmids from the donor cell to the recipient cell, mediated by bacteriophages (bacterial
viruses). After the bacteriophage attaches to a receptor on the cell surface, the DNA is
introduced into the bacterium. The bacteriophage exploits the metabolic processes of the
cell to replicate viral DNA and produce viral proteins. Following the formation of new
bacteriophages inside the bacterial cell, it undergoes lysis—the lytic cycle. Phage DNA
can also become incorporated into the bacterial chromosome (prophage), which is called
lysogeny [8,15]. Among transposition elements capable of changing places in the genome,
we can distinguish insertion sequences (IS) and transposons (Tn). Insertion sequences are
DNA segments containing a gene coding for transposase, surrounded on both sides by
inverted repeat sequences. This enzyme allows insertion elements to move to any site
in DNA. Resistance genes can also be located on transposons, sometimes called ‘jump-
ing genes’. Among transposons (Tn) we can distinguish composite transposons, which
consist of two insertion sequences located on either side of genes encoding resistance to
antibiotics or other genes not associated with movement of the transposon (e.g., Tn10). In
non-composite transposons (type Tn3), genes encoding additional traits are surrounded
by short inverted sequences, and transposition is replicative and requires the products of
both genes. Conjugative transposons differ from classic transposons in that they can be
transferred not only within the DNA of a single cell, but also between cells. They occur in a
form integrated with a plasmid or bacterial chromosome. In response to certain signals,
Antibiotics 2022, 11, 1079 4 of 40
these transposons form circular forms that are incapable of replication. The transfer is
similar as in the case of conjugative plasmids [8]. In the evolution of multi-drug resistance
in bacteria, an important role is also ascribed to integrons, which can be located in both bac-
terial chromosomes and plasmids. This is a specific self-translocational type of specialized
carriers of genetic information, whose special property is the ability to combine resistance
genes into cassettes, which are transferred together in this form to recipient cells [7].
Given the global threat posed by the widespread phenomenon of multi-drug resistance
among bacteria which are dangerous for humans and animals, the subject of this study is
the mechanisms of resistance of bacteria isolated from human and animals. This review also
presents the percentage range of the occurrence of drug resistance among selected bacteria.
3. Mechanisms of Transfer of Resistance Based on Examples of Various Species

of Bacteria
3.1. Campylobacter spp.
Campylobacter, especially C. jejuni, is recognized as one of the most common causes of
food-borne gastroenteritis in humans [16,17]. Poultry has been shown as the most important
source of these bacteria and the main transmission route of Campylobacter to humans is the
handling of contaminated food, especially of chicken meat [16–18]. However, ruminants,
especially cattle, and pigs are also responsible for human C. jejuni and, to a lesser extent
C. coli, infections [19,20]. The majority of campylobacteriosis cases are usually self-limiting
and do not require any antibacterial treatment. However, the medical interventions are
needed in very young or elderly patients, pregnant women, or when the complications
such as e.g., Guillain-Barré syndrome develop [21]. In these cases, the macrolides (e.g.,
erythromycin) are usually the antimicrobials of the first choice, whereas fluoroquinolones
(e.g., ciprofloxacin) or tetracyclines are alternative options [22].
3.1.1. Resistance to Fluoroquinolones

AMR of Campylobacter, especially to fluoroquinolones (e.g., ciprofloxacin), has recently
emerged [23]. Moreover, co-resistance to fluoroquinolones and macrolides (e.g., erythromycin),
other antimicrobials of choice for treatment of Campylobacter infections, has recently been
noted [24]. Furthermore, some studies have shown that infections with quinolone- or
erythromycin-resistant Campylobacter cause longer and more severe disease, as well as an
increased risk of an invasive form of the illness or even death [25]. Several molecular mecha-
nisms of antimicrobial resistance have been identified in Campylobacter [26–28]. One involves
mutations in the genetic material which lead to the development of total or at least partial
resistance to various antimicrobials [29]. Campylobacter can acquire antibiotic resistance-
encoding sequences via horizontal transfer of genes from other bacteria of the same or
different species [26]. Antimicrobial resistance can also be acquired through spontaneous
mutations in genes resulting in genetic markers responsible for chromosomally encoded
resistance to fluoroquinolones or macrolides [30]. Mutations responsible for Campylobacter
resistance to fluoroquinolones are mainly identified in the quinolone resistance-determining
region (QRDR) of DNA gyrase (topoisomerase II) encoded by the gyrA and gyrB genes, re-
sponsible for synthesis of two subunits of the enzyme (subunits A and B, respectively) [31].
Point mutations in the gyrA sequence at positions Thr-86, Asp-90, and Ala-70 have been
linked to fluoroquinolone resistance in C. jejuni [32]. Among these, the Thr-86-Ile change in
the gyrA gene is the most commonly observed mutation responsible for high-level resis-
tance in fluoroquinolone-resistant Campylobacter, whereas the Thr-86-Lys and Asp-90-Asn
mutations are less common and are associated with intermediate fluoroquinolone resis-
tance [33]. Double point mutations of the gyrA gene together with Asp-85-Tyr, Asp-90-Asn,
or Pro-104-Ser have also been reported [34]. A high level of resistance to fluoroquinolones
in Campylobacter can also be due to the synergistic effect of the gyrA mutation combined
with the action of the CmeABC multidrug efflux pump encoded by an operon consisting of
three genes, cmeA, cmeB, and cmeC, responsible for the expression of a periplasmic fusion
protein, an inner membrane drug transporter, and an outer membrane protein, respec-
Antibiotics 2022, 11, 1079 5 of 40
tively [35]. The CmeABC efflux pump is regulated by the CmeR repressor, which is highly
conserved in nature. An insertional cmeR Campylobacter mutant strain showed overex-
pression of CmeABC pump components, and consequently a decrease in the intracellular
concentration of antibiotic. Furthermore, when this efflux pump had been blocked, the
minimum inhibitory concentration (MIC) values for fluoroquinolones (e.g., ciprofloxacin)
were reduced to the level identified in susceptible strains, even in the presence of mutations
in the gyrA gene [32]. Recently, Yao et al. using whole genome sequencing showed that the
cmeABC genes are globally distributed among human and poultry C. jejuni which may be
horizontally transferred between strains of different origins [36].
3.1.2. Resistance to Macrolides

The frequency of mutations of the genes responsible for macrolide resistance in
Campylobacter is much less common than in the case of fluoroquinolone resistance. More-
over, emergence of high-level resistance may require multiple mutation steps; thus, macrolide-
resistant Campylobacter mutants usually develop more slowly under selective antibiotic
pressure than under the influence of fluoroquinolones, so they need prolonged exposure to
macrolide antimicrobial agents [37]. Resistance of Campylobacter to this class of antibiotics
is usually the result of modification of the ribosome target binding site by mutation of 23S
rRNA at positions 2074 (A2074C, A2074G, or A2074T), 2075 (A2075G or A2075C), or both of
the adenine residues in all three copies of this gene (rrnB operon) [37]. However, high-level
macrolide resistance is mainly associated with a modification at A2075G in domain V of
23S rRNA. Such resistance mechanisms to erythromycin have also been shown to corre-
spond with cross-resistance to other macrolides and related drugs of the lincosamide and
streptogramin classes [29].
Resistance of Campylobacter isolates to macrolides may also be the result of modifica-
tions of the ribosomal subunit proteins L4 and L22 of 50S ribosome, encoded by the rplD
and rplV genes, respectively [33]. The G-to-A transition at nucleotide 221 of the rplD gene
causes a glycine to asparagine substitution at position 74 of the L4 protein sequence [38]. In
the case of the L22 protein, the main cause of macrolide resistance is duplication at positions
292 and 256 in the rplV gene [39]. Additionally, the presence of the emerging ermB gene
has been linked to macrolide resistance in Campylobacter [30]. This gene encodes an rRNA
methylase which produces cross-resistance to macrolides, lincosamides and streptogramin
B [40]. The ermB-encoded enzyme acts on the 23S rRNA gene by methylating an adenine
residue that impedes antibiotic binding to the ribosome [41]. Comparative genomic anal-
ysis identified identical ermB sequences among Campylobacter and other bacterial species
from animals and humans, which suggests possible horizontal transfer and wide dissem-
ination of antimicrobial resistance to macrolides, which may reduce the effectiveness of
antimicrobial therapy.
3.1.3. Resistance to Tetracyclines

Resistance of Campylobacter to tetracyclines is mainly conferred by the tet(O) gene
located on the pTet plasmid and coding for the ribosomal protection protein tet(O). However,
the high-level resistance of these bacteria to tetracycline also depends on the CmeABC efflux
pumps, alone or in connection with the plasmid-encoded tet(O) gene [42]. The tet(O) gene
is located on a self-transmissible plasmid of molecular size from 45 to 58 kb [43]. However,
location of this sequence on the chromosome has also been reported among tetracycline-
resistant C. jejuni without the tet(O)-positive plasmid [44]. Furthermore, the presence of
an insertion element IS607 on the tet(O)-carrying plasmid in Campylobacter, which was
similar to IS607 present on the chromosome of Helicobacter pylori, may suggest that mobile
genetic elements other than transmissible plasmids may be involved in the acquisition and
dissemination of tet(O) tetracycline resistance genes in other bacterial species. Sequence
analysis of G-C content also suggests that this gene was probably acquired by Campylobacter
via horizontal gene transfer from Streptomyces, Streptococcus, or Enterococcus spp. Since the
conjugative tet(O)-carrying plasmid is widely prevalent among Campylobacter, it is possible
Antibiotics 2022, 11, 1079 6 of 40
that conjugation has contributed to the spread of tetracycline resistance genes among these
and other bacterial species [27].
3.1.4. Resistance to β-Lactams

The above-mentioned multidrug efflux pumps, such as CmeABC, also play a role in
the prevalence of resistance of Campylobacter to β-lactam antibiotics, e.g., ampicillin [35].
A significant increase in susceptibility to ampicillin has been demonstrated in CmeABC-
inactivated C. jejuni mutants, and a decrease in susceptibility in CmeABC-overexpressing
mutants [45]. Another mechanism of β-lactam resistance in Campylobacter is the produc-
tion of chromosomally encoded β-lactamase OXA-61 [28]. The expression level of this
gene modulates the susceptibility of the bacteria to this class of antimicrobials, e.g., a
single nucleotide mutation (G–T transversion) in the promoter region of blaOXA-61 led to
overexpression of the gene and consequently to a high increase in β-lactam resistance in
C. jejuni [46]. Campylobacter bacteria are capable of intrinsic production of β-lactamases
in the absence of selective (antibiotic) pressure. The blaOXA-61 gene has been shown to be
widely distributed among Campylobacter isolated from poultry but has also been identified
in isolates from non-food producing animals and environments [47,48]. On the other hand,
β-lactam antibiotics are known to have limited efficacy against Campylobacter, and resis-
tance to this class of antimicrobials appears to be mediated by both intrinsic resistance and
β-lactamase production [26]. Oral β-lactams, such as co-amoxiclav, could be an appropriate
choice when Campylobacter is resistant to both fluoroquinolones and macrolides [28].
The spread of various genetic determinants responsible for Campylobacter resistance to
quinolones, macrolides, and tetracyclines is very common and increases the prevalence of
antimicrobial-resistant Campylobacter isolated from humans, foods of animal origin, and
animals (Table 1). Resistance to fluoroquinolones and tetracyclines is very common among
clinically- and broiler-associated Campylobacter, while prevalence of erythromycin-resistant
strains is fairly low, or moderate, in Europe [24]. Resistance to quinolones is an especially
important concern in many countries, including Poland [48].
Transmission of antimicrobial-resistant Campylobacter strains to humans usually oc-
curs via consumption of contaminated food products, especially of poultry origin [49].
Interestingly, high levels of resistance to tetracyclines among clinical isolates have often
been observed despite the fact that these antibiotics are not used for campylobacteriosis
treatment in humans in Europe [24]. However, antibiotics of this class are broadly applied
in veterinary medicine for food-producing animals, which are an important reservoir of
Campylobacter tetracycline-resistant strains [47,50]. On the other hand, the common use of
antibiotics in veterinary medicine does not always correlate with AMR of Campylobacter
recovered from animals treated in this manner [28]. Although the use of tetracyclines and
macrolides has decreased in recent years, the percentages of these antimicrobial-resistant
strains have remained stable or even increased [51]. On the other hand, the reverse trend
has been noted for fluoroquinolones.
Based on antimicrobial resistance data, especially regarding the high prevalence of
fluoroquinolone, tetracycline, and β-lactam resistance, as well as the lower but increasing
resistance to macrolides, constant monitoring of the susceptibility of Campylobacter to
antimicrobial agents is needed. Such measures, especially related to food-producing
animals such as poultry, have been implemented in European Union member states since
2014 [52]. This will help to reduce antimicrobial-resistant Campylobacter strains among
the main reservoirs of these bacteria and prevent the spread of resistance genes between
animals as well as between animals and humans.
Antibiotics 2022, 11, 1079 7 of 40
Table 1. Examples of prevalence of antimicrobial-resistant Campylobacter spp. isolated from various

sources.
Resistance to Antimicrobials (Resistance

Source of Isolates Percentage of Isolates with Resistance Genes References
Genes)
13.8 (Burkina Faso); 20.1 (Australia); 50.0 (Ethiopia);

Sangaré et al. [53]; Chala et al. [54]; Meistere et al. [49]; Wieczorek et al. [55];
Humans 55.8–85.7 (BE); 72.2–100 (Lithuania); 77.4 (Peru); 85.2 (PL);
Elhadidy et al. [56]; Zhang et al. [57]; Wallace et al. [58]; Schiaffino et al. [59]
89.4 (China)
Fluoroquinolones (gyrA) 0–60.0 (China); 3.7–8.0 (USA); 25.0–100 (Ethiopia); 36.4–100 Tang et al. [60]; Chala et al. [54]; Béjaoui et al. [61]; Nguyen et al. [62]; Meistere et al.
Animals and food (Tunisia); 47.6–100 (Lithuania); 60.0–96.1 (Poland); 65.0–95.3 [49]; Tenhagen et al. [50]; Wieczorek and Osek [48]; Andrzejewska et al. [63];
(Germany); 71.0 (Kenya) Bailey et al. [64]
0 (Lithuania); 0.6 (Poland); 1.8 (Australia); 2.0–28.6

Humans (Belgium); 5.3 (Peru); 10.3 (Burkina Faso); 24.0 (China);
Elhadidy et al. [56]; Zhang et al. [57]; Wallace et al. [58]; Schiaffino et al. [59]
80.0 (Ethiopia)
Macrolides
0–1.4 (Lithuania); 0–70.0 (China); 0–74.4 (Poland); 0–64.5 Tang et al. [60]; Chala et al. [54]; Béjaoui et al. [61]; Nguyen et al. [62]; Meistere et al.
(ermB; efflux pumps)
Animals and food (Germany); 1.5–2.8 (USA); 25.0–100 (Ethiopia); 25.8–51.6 [49]; Tenhagen et al. [50]; Wieczorek et al. [48]; Andrzejewska et al. [63];
(Kenya); 90.9–100 (Tunisia) Bailey et al. [64]
10.3 (Burkina Faso); 15.6 (Australia); 49.7–85.7 (Belgium);

Humans 55.5–100 (Lithuania); 55.8 (Peru); 70.0 (Ethiopia); 70.3
Zhang et al. [57]; Wallace et al. [58]; Schiaffino et al. [59]
(Poland); 93.3 (China)
Tetracyclines (tet(O)) 0–64.0 (China); 3.8–77.0 (Poland);14.0–66.7 (Lithuania); Tang et al. [60]; Chala et al. [54]; Béjaoui et al. [61]; Nguyen et al. [62];
Animals and food 32.5–92.1 (Germany); 55.6–100 (Ethiopia); 57.9–78.1 (Poland); Meistere et al. [49]; Tenhagen et al. [50]; Wieczorek et al. [53];
65.3–81.6 (USA); 71.0 (Kenya); 100 (Tunisia) Andrzejewska et al. [63]; Bailey et al. [64]
3.2. Enterococcus spp.

Bacteria of the genus Enterococcus are part of the natural gut microbiota in human
and animals.
In human Enterococcus spp. are generally associated with incidences of intra-abdominal
infections (IAI) and represent the second most common cause of infection. The Enterococcus
bacteria are isolated from human with endocarditis, bloodstream infection, wound and
surgical-site infection, as well as intra-abdominal and urinary tract infection [65]. This
bacteria has also been associated with chronic periodontitis and persistent endodontic in-
fections [66]. Typically, uncomplicated wound infections, urinary tract infections and most
intra-abdominal infections are treated with a single antibiotic directed against enterococci.
Infections caused by Enterococcus spp. represent a serious threat to human and animal
health due to difficulties in treatment. These bacteria are a very able to transfer of antimicro-
bial resistance genes and for this reason they are often resistant to many antimicrobials [67].
In clinical practice, combination therapy with a cell wall-activating agent (ampicillin,
penicillin) and a synergistic aminoglycoside (high doses of gentamicin) is undertaken to
treat serious enterococcal infections in critically ill patients and those with evidence of sepsis,
as well as patients with endocarditis, meningitis, osteoarthritis. Once there is resistance
to one antimicrobial from these groups of antibiotics, the drug of so-called last resort
is vancomycin. For infections with vancomycin-resistant Enterococcus strains, linezolid,
daptomycin, quinupristin/dalphopristin and tigecycline are used for treatment [68].
In veterinary medicine, the therapeutic management of Enterococcus spp. infections is
mainly based on monotherapy with antibiotics selected based on the results of drug suscep-
tibility testing, the location of the infection, and the species of affected animals [67,69]. This
is related to the limited possibilities of using antibiotics in animals, especially those intended
for consumption [67,70]. Such treatment appears to be effective, although randomized,
controlled trials evaluating the efficacy of such treatment are lacking.
The last decade has seen more frequent reports of the role of Enterococcus spp. in
the pathology of bird diseases. They have natural resistance to a number of antibi-
otics used in treatment, including β-lactam antibiotics, all generations of cephalosporins
and sulphonamides. They show lower resistance to aminoglycosides, lincosamides and
quinolones [65] Irrational use of antimicrobials has led to an increase in the population of
multi-drug resistant Enterococcus strains.
3.2.1. Resistance to β-Lactam Antibiotics

Enterococci have natural, innate resistance to β-lactam antibiotics due to their low
affinity for penicillin-binding proteins—PBP5 in E. faecium and PBP4 in E. faecalis [71].
This resistance varies depending on the type of β-lactams, e.g., penicillin has the highest
activity against enterococci, that of carbapenems is somewhat lower, and the activity of
cephalosporins is the lowest. Another resistance mechanism associated with penicillin-
Antibiotics 2022, 11, 1079 8 of 40
binding proteins is sometimes observed in the case of bacteria which acquire a very high
level of resistance to β-lactam antibiotics in comparison to wild strains. In some bacteria,
resistance to β-lactams is associated with overproduction of PBP5 surface proteins. An
example is overproduction of PBP5 by some penicillin-resistant strains of E. hirae. The
gene pbp5 in E. hirae is under the control of the psr gene [72]. Inactivation of psr through
deletion or mutation leads to an increase in the number of copies of PBP5, and thus to
saturation of all molecules of this protein. Some enterococci have a completely different,
less common mechanism of resistance to β-lactams, involving synthesis of β-lactamases—
enzymes hydrolysing the β-lactam ring in the antibiotic molecule. The hydrolysed antibiotic
is inactivated and does not inhibit the enzymatic functions of surface PBPs. The gene
determining expression of β-lactamases is located on a plasmid and usually occurs with a
gene encoding resistance to gentamicin. B-lactamases are most often produced in small
amounts. Thus, when the number of bacteria is small, the MIC values for penicillin
and ampicillin may be at a level corresponding to that of bacteria that are susceptible to
these antibiotics [73].
3.2.2. Resistance to Inhibitors of the Third Step of Peptidoglycan Synthesis—Glycopeptides

The most important process providing bacteria with resistance to glycopeptides is
weakening of the bonds between molecules of the antibiotic and receptors located in
the cell wall. Enterococci, both susceptible and resistant to vancomycin, possess specific
complexes composed of peptidoglycans and pentapeptides outside their cell membrane.
These are target structures to which glycopeptide antibiotics bind. The above-mentioned
pentapeptides consist of tripeptide precursors to which dipeptides attach. In the case of
vancomycin-susceptible strains, this is D-alanyl-D-alanine (D-Ala-D-Ala), while in the case
of vancomycin-resistant enterococci (VRE) the terminal amino acid D-alanine is replaced
with D-serine (D-ser) or D-lactate (D-lac). The D-alanine to D-serine substitution results in
changes in the conformation of bonds with molecules of the antibiotic, significantly weaken-
ing it. If D-lactate is attached in place of D-alanine, the number of bonds with vancomycin
decreases. Strains containing D-Ala-D-Ser dipeptides are susceptible to teicoplanin and
show resistance to low concentrations of vancomycin. However, when peptidoglycan
precursors contain D-Ala-D-Lac dipeptides, they are highly resistant to vancomycin [74].
Structures organized in this manner take part in cell wall synthesis. Due to binding of
vancomycin to the pentapeptide molecule, it is blocked, stopping cell wall synthesis. In the
second case, binding of the antibiotic to the peptidoglycan precursor is limited, and cell wall
synthesis may take place despite the presence of vancomycin. Enterococci are neither phe-
notypically nor genotypically homogeneous in terms of resistance to vancomycin. Based
on the level of resistance to vancomycin, the capacity to induce it, and cross-resistance to
vancomycin and teicoplanin, seven phenotypic classes of enterococci are distinguished:
VanA, VanB, VanC, VanD, VanE, VanG [75] and VanL [76]. Within each of the types VanB
and VanC, three subtypes are distinguished (VanB1, VanB2, VanB3; VanC1, VanC2, VanC3).
The most important phenotypes in clinical practice are VanA and VanB.
Type A resistance (VanA). This acquired, inducible resistance to high concentrations
of vancomycin (MIC 64–100 µg/mL) and teicoplanin (MIC 16–512 µg/mL) is most com-
mon in E. faecalis, E. faecium, E. durans, E. raffinosus, E. hirae, E. avium, E. casseliflavus, and
E. mundtii, but also occurs in E. gallinarum [77,78]. The terminal fragment of D-Ala-D-Ala
is replaced with dipeptide D-Ala-D-Lac, which prevents binding of the antibiotic even at
very high concentrations. Genes are transferred by transposon Tn1546 present on a plasmid
or chromosome [75].
Type B resistance (VanB). The VanB phenotype is characterized by inducible resis-
tance to vancomycin at various levels (MIC 4–1024 µg/mL) with susceptibility in vitro
to teicoplanin (MIC 0.5–1 µg/mL). Dipeptide D-Ala-D-Ala is replaced with D-Ala-D-Lac,
as in phenotype VanA. It is found in the species E. faecium, E. faecalis, E. durans and
E. gallinarum [79,80]. Based on DNA sequences of genes encoding VanB ligase, three sub-
types are distinguished within this phenotype: VanB1, VanB2, and VanB3 [77]. However,
Antibiotics 2022, 11, 1079 9 of 40
no relationship has been shown between a given subtype and the level of resistance to
vancomycin and teicoplanin.
Type C resistance (VanC). This is natural resistance occurring in motile species of ente-
rococci: E. gallinarum (vanC1) [79], E. casseliflavus (vanC2) and E. flavescens (vanC3) [81]. It is
both inducible and constitutive. Alongside D-Ala-D-Ala fragments, D-Ala-D-Ser peptides
appear in a 1:3 ratio. This phenotype is characterized by resistance to low concentrations of
vancomycin (MIC 4–32 mg/L) and susceptibility to teicoplanin (MIC < 1 mg/L).
Type D resistance (VanD) results from production of peptidoglycan precursors ter-
minating in D-alanyl-D-lactate, but the genetic background of strains described thus far
is varied [82]. In the case of Enterococcus faecium BM439, insertion of five base pairs has
been found in the structural gene of ligase, while in E. faecium BM4416 the mutation was
due to insertion IS19 in the gene ddl. VanD enterococci have constitutive resistance to
relatively high concentrations of vancomycin (MIC 64 µg/mL) and to low concentrations
of teicoplanin (MIC 4 µg/mL).
Type E, G and L resistance (VanE, VanG and Van L). VanE is an acquired type of resis-
tance found in E. faecalis strain BM4405, showing a low level of resistance to vancomycin
(MIC 16 µg/mL) and sensitivity to teicoplanin. This strain produces peptidoglycan precur-
sors terminating in D-alanyl-D-serine [83]. The acquired VanG phenotype is characterized
by resistance to vancomycin (MIC 16 mg/mL) and susceptibility to teicoplanin (MIC
0.5 mg/mL). This resistance results from production of peptidoglycan precursors termi-
nating in D-ala-D-ser [84]. The VanL phenotype has been found in E. faecalis N06-0364
resistant to vancomycin at a level of MIC 8 µg/mL. This resistance results from produc-
tion of peptidoglycan precursors terminating in D-ala-D-ser. The vanL gene is similar in
structure to the vanC operon, but VanT serine racemase is encoded by two separate genes:
vanTmL (membrane-binding) and vanTrL (racemase) [76]. The VanD, VanE, VanG and VanL
phenotypes are extremely rare. No clinical strains with these resistance phenotypes have
been recorded in Poland.
3.2.3. Resistance to Aminoglycosides

Bacterial resistance to aminoglycoside antibiotics is associated with the activity of
enzymes that inactivate the antibiotic, enzymatic modification of 16S rRNA, a change in
the permeability of bacterial membranes for the drug, or enzymatic modification of the
antibiotic. The natural mechanism of resistance to low concentrations of aminoglycosides in
enterococci is associated with low permeability of bacterial cell membranes for molecules of
the antibiotic and precludes the use of these drugs in monotherapy. However, the combined
use of an aminoglycoside with penicillin or glycopeptides is effective, provided the bacteria
are susceptible in vitro to these groups of antibiotics [79]. Resistance to high concentrations
of aminoglycosides—the HLAR (high-level aminoglycoside resistance) phenotype—is an
acquired resistance. In these cases, bacteria are able to synthesize specific aminoglycoside-
modifying enzymes (AME), which include phosphotransferases (APHs), acetyltransferases
(AACs) and nucleotidyltransferases (ANTs). In the acylation and phosphorylation pro-
cesses, enzymes modify molecules of the antibiotic, giving it a different conformation that
prevents the drug from binding to its target site (30S ribosomal subunit). Expression of
AMEs depends on genes located on mobile genetic elements—plasmids, which can easily
spread among various strains [85]. Currently over 60 enzymes able to modify aminogly-
coside molecules have been identified. However, there are Enterococcus strains that are
resistant to aminoglycosides, which produce the bifunctional enzyme AAC(60 )-APH(2”),
encoded by the gene aac(60 )-Ie-aph(2”)-Ia. This protein has a broad spectrum of activity,
because it can modify many aminoglycoside antibiotics, except for streptomycin. aac(60 )-
Ie-aph(2”)-Ia mainly mediates resistance to gentamicin, tobramycin, amikacin, kanamycin,
netilmicin and dibekacin. More than 90% of Enterococcus strains isolated from clinical cases
show a high level of resistance to gentamicin (MIC ≥ 2000 µg/mL), due to the presence of
aac(60 )-Ie-aph(2”)-Ia, while less than 10% possess aph(2”)-Ic, aph(2”)-Id or aph(2”)-Ib [86].
Antibiotics 2022, 11, 1079 10 of 40
The HLSR (high-level streptomycin resistance) phenotype means a high level of

resistance to streptomycin -MIC > 1024 µg/mL EUCAST [87], which results from the
activity of nucleotidyltransferase ANT(60 ) or ANT(3”), modifying streptomycin, or to
mutations in the genes encoding components of 30S ribosomal subunit. Due to mutations
of genes responsible for ribosomal proteins, a new ribosomal protein is produced. The
mutated protein S12, which is an aminoglycoside receptor, has very low affinity for this
class of antibiotics. In this way Enterococcus bacteria with mutated ribosomal protein S12
acquire resistance to streptomycin.

Tetracyclines inhibit protein synthesis (by blocking the bacterial 30S ribosomal subunit)
and disturb energy processes in bacterial cells. Antibiotics can be actively removed from
the cytoplasm by special efflux pumps resulting from the expression of genes tet(K) and
tet(L) and ribosome conformation. Genes tet(M), tet(O) and tet(S) encode proteins which
affect resistance by protecting the ribosome. This involves binding resistance proteins to
the ribosome, followed by a change in the conformation of the ribosome, which limits
binding of tetracyclines. The most common gene of resistance to tetracyclines is tet(M),
which is located on the chromosome and is usually transferred on transposon Tn916 or
similar conjugative transposons, but sometimes on conjugative plasmids [88].
3.2.5. Resistance to Macrolides, Lincosamides and Streptogramins

The first described mechanism of resistance to macrolides involved post-transcription
modification of 23S rRNA resulting from the activity of adenine-N6 -methyltransferase.
Enzymes from this group transfer one or two methyl residues to an adenine molecule in 23S
rRNA, resulting in N6 -methyladenine or N6 ,N6 -dimethyladenine. This reduces binding
not only of erythromycin in the ribosome, but also of other macrolides (azithromycin and
clarithromycin) and of lincosamides and streptogramin B. This mechanism is encoded by
the gene erm(B), or less often by erm(A), and the phenotype is called ‘MLSB ’ (macrolide-
lincosamide-streptogramin B) [89]. Resistance to macrolides and lincosamides can also
be determined by the ability of bacteria to produce specific enzymes inactivating antibi-
otics. This inactivation can be the result of cleavage of the lactone ring of the macrolide
by esterase or modification of its structure by enzymes with transferase activity (acetyl-
transferase, nucleotidyltransferase, or phosphotransferase), phosphorylase or hydrolase.
These mechanisms usually give the bacterial cell resistance to only one of three classes of
antibiotics belonging to this group (macrolides, lincosamides, or streptogramins), or to
only one kind of them (e.g., streptogramin B). Some Enterococcus spp. bacteria have the
sat gene encoding acetyltransferases which inactivate group A streptogramins. E. faecalis
is naturally resistant to clindamycin (lincosamides), quinupristin (streptogramin B) and
dalfopristin (streptogramin A), due to expression of the gene lsa. This gene is structurally
similar to the ABC (ATP-binding cassette) transporters, suggesting ATP-energized efflux as
the likely resistance mechanism against clindamycin and dalfopristin. The gene was found
in 180/180 strains of E. faecalis and in none of 189 other enterococci, which suggests that it
is innate in E. faecalis [90].
3.2.6. Resistance to Antimetabolites—Sulphonamides and Trimethoprim

Sulphonamides inhibit synthesis of dihydrofolic acid, acting as competitive inhibitors
of the enzyme dihydropteroate synthase (DHPS). Production of dihydropteroate synthase
by bacteria causes their affinity for the drug to decrease. In addition, overproduction of
p-aminobenzoic acid causes it to compete directly for access to the active centre of DHPS.
The action of the antibiotic causes some bacteria to produce an alternative metabolic path-
way, which replaces the pathway blocked by the antibiotic. This phenomenon is called a
‘bypass mechanism’ and is recognized as a means of acquiring resistance to sulphonamides
and trimethoprim. Most bacteria are not able to absorb folacin from the environment, so
they need to synthesize it to produce nucleic acids. The combination of trimethoprim and
Antibiotics 2022, 11, 1079 11 of 40
sulfamethoxazole inhibits two consecutive steps in the tetrahydrofolate synthesis pathway,

which blocks synthesis of folic acid and synergistically destroys a broad spectrum of bacteria.
Enterococcus bacteria have the exceptional ability to absorb folic acid from the environment,
thereby bypassing the effect of the trimethoprim/sulfamethoxazole combination [91].

Quinolones inhibit bacteria by interacting with type II topoisomerase, DNA gyrase
and topoisomerase IV, which are essential to replication of bacterial DNA. DNA gyrase
consists of two subunits called gyrA and gyrB. Topoisomerase IV, which is the main target
of quinolones in gram-positive bacteria, consists of two subunits called parC and par E,
which are homologous to gyrA and gyr B. Resistance of enterococci to fluoroquinolones
is determined by point mutations on chromosomes. Therefore, genes of resistance to
fluoroquinolones cannot be transferred to other bacteria via transfer of genetic material.
The frequency of this mutation in the bacterial genome is determined by the intensity
of antibiotic treatment with drugs from this group. The most common mutations are
modifications of genes encoding topoisomerase II (gyrase) and topoisomerase IV. E. faecalis
with a mutation in parC but not in gyrA has shown intermediate resistance to quinolones.
The minimum inhibitory concentration (MIC) of quinolones for this isolate was higher than
the MIC for E. faecalis without a mutation in the parC or gyrA gene, but lower than the MIC
for E. faecalis with mutations in both parC and gyrA [92].
Among 911 tested Enterococcus spp. isolates (mainly E. faecalis and E. faecium) from
poultry, the highest resistance was shown for trimethoprim/sulfamethoxazole (88%), ty-
losin (71.4%), enrofloxacin (69.4%), doxycycline (67.3%) and lincomycin with spectinomycin
(56.1%). Enterococci isolated from wild birds showed the highest resistance to lincomycin
(100%), tetracycline (48%), erythromycin (44%) and ciprofloxacin (22%). These birds also
showed resistance to high concentrations of streptomycin and kanamycin (in 19% and
15% of isolates, respectively) [93]. Another study [94], analysing the drug susceptibility of
227 enterococci isolated from animals, fresh food, hospital and municipal wastewater, and
seawater in Poland showed the highest susceptibility to penicillin, ampicillin, vancomycin,
teicoplanin, tigecycline, linezolid and daptomycin. Some of these isolates showed resistance
to high concentrations of gentamicin (1.3%) and/or streptomycin (9.2%) and were often
not susceptible to rifampin and tetracycline (81.9% and 53.7%, respectively). Enterococci
isolated from sick dogs (urinary tract infections in own study) St˛epień-Pyśniak et al. [69]
and healthy dogs (gastrointestinal tract) in Italy showed a high level of resistance to amino-
glycosides (streptomycin 94.1%, neomycin 90.2%, gentamicin 68.6%), fluoroquinolones
(enrofloxacin 74.5%, ciprofloxacin 66.7%), oxacillin (98%), clindamycin (84.3%), tetracycline
(78.4%) and quinupristin-dalfopristin (78.4%) [69]. Clinical Enterococcus spp. isolates from
humans in Italy showed high resistance to ampicillin (84.5%), ampicillin/sulbactam (82.7%)
and imipenem (86.7%) as well as to high-level gentamicin and streptomycin [95].
3.3. Escherichia coli

Escherichia coli (E. coli) is a common member of the natural intestinal microflora of
humans and animals. Within the E. coli species, apart from commensals commonly col-
onizing the intestines of mammals and birds, there are also intestinal pathogenic E. coli
(IPEC) and extraintestinal pathogenic E. coli (ExPEC) strains. IPEC bacteria are associated
with infections of the gastrointestinal tract. Several pathotypes can be distinguished among
IPEC strains: enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enterohaem-
orrhagic E. coli (EHEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC),
adherent invasive E. coli (AIEC), and diffusely adherent E. coli (DAEC) [96]. ExPEC strains
cause infections in extraintestinal anatomic sites, and in this group include: uropathogenic
E. coli (UPEC) associated with urinary tract infection in human and animals, neonatal
meningitis-associated E. coli (NMEC), septicaemic E. coli (SePEC) causing systemic infection
in human and animals, avian pathogenic E. coli (APEC) that cause avian colibacillosis, and a
potentially emerging ExPEC lineage named endometrial pathogenic E. coli (EnPEC) [97,98].
Antibiotics 2022, 11, 1079 12 of 40
E. coli infections in animals are subjected to various pharmaceutical treatments. For

instance, broad-spectrum cephalosporins and fluoroquinolones are commonly used to
treat bovine mastitis [99]. One of the antibiotics used to treat colibacillosis in poul-
try is enrofloxacin, which belongs to fluoroquinolones [100]. Antibiotics belong to β-
lactams, polymyxins, tetracyclines and macrolides have been reported to be the most
frequently used antibiotics in European pig production, mainly used to treat intestinal and
respiratory disorders [101].
One of the most important mechanisms of resistance to antibiotics in Enterobacteriaceae
is the production of enzymes capable of hydrolysis of penicillin, cephalosporin and
monobactams. These enzymes are called extended-spectrum β-lactamases (ESBLs). The
mechanism was detected in 1983 in Klebsiella pneumoniae. Initially, bacteria with ESBLs
were known only as aetiological agents in hospital-acquired infections. They are currently
also detected as a cause of community-acquired infections, and cases of carriage of these
bacteria are noted as well.
The mechanism, which was first diagnosed in 2008 in K. pneumoniae and E. coli, involves
production of an enzyme from the metallo-β-lactamase group. It confers resistance to many
β-lactam antibiotics, including carbapenems. Carbapenems are regarded as drugs of last
resort and are used mainly to treat diseases caused by bacteria resistant to other antibiotics.
Substances from this group are especially important due to their broad spectrum of activity.
Carbapenems exhibit activity against aerobic and anaerobic, gram-positive, and gram-
negative bacteria [102].

Production of β-lactamases by bacteria can be induced or constitutive. Constitutive
enzymes are continually produced by cells, and their level is not dependent on the presence
of an antibiotic in the environment but is a fixed trait of the strain or species of bacteria. The
presence of constitutive β-lactamase, produced in an adequate amount, can be the cause
of natural resistance to an antibiotic to which it has affinity. The condition of production
of induced β-lactamases by bacteria is activation by the antibiotic of β-lactam present in
the environment. Synthesis of these enzymes takes place until the activator is removed
from the environment, and thus it determines temporary resistance. Mutations may occur
during induction, so that the induced β-lactamase is continually produced by the bacteria,
even after the inductor is removed, resulting in permanent resistance to the antibiotic [103].
Resistance of E. coli to β-lactams is mainly associated with the production of extended-
spectrum β-lactamases (ESBL), which are capable of hydrolysing penicillins, cephalosporins
(except for cephamycin) and monobactams, but are not able to break down carbapenems,
and their activity is inhibited by β-lactamase inhibitors (clavulanic acid, sulbactam, and
tazobactam) [104]. B-lactamases are present in the periplasmic space, most often encoded
by large plasmids (e.g., IncF, IncI1, IncN, IncHI1, and IncHI2 [105]), which facilitates their
rapid and uncontrolled spread. B-lactamases are a highly diverse group of enzymes in
terms of structure and substrate profile, i.e., activity against penicillin, cephalosporins
and carbapenems [106]. Several types of ESBLs are distinguished: CTX-M, SHV, TEM,
OXA, PER, VEB, BES, GES, SFO, TLA and IBC [107]. The enzyme CTX-M exhibits strong
hydrolytic activity against cefotaxime, encoded by the gene blaCTX-M , usually located
on a plasmid e.g., IncF, IncN, INcK and Incl1 [105]. OXA enzymes, which hydrolyse
carbapenems, are mainly found in Enterobacterales (including E. coli) and are coded by
blaOXA plasmid genes. ESBLs are most widespread among Enterobacteriaceae, including
E. coli. Apart from those produced by hospital-acquired strains, they are increasingly
observed in strains inducing community-acquired infections, as well as in bacterial strains
isolated from animals [108]. It should be noted that in many E. coli isolates of animal origin,
a common location was identified for the mcr-1 gene determining resistance to colistin and
bla genes encoding extended-spectrum β-lactamases.
Antibiotics 2022, 11, 1079 13 of 40
AmpC β-Lactamases
AmpC cephalosporins break down all penicillins and most cephalosporins (mainly
first and second generation) except for cefepime, but do not hydrolyse aztreonam, although
some of them can bind it [109]. These enzymes do not hydrolyse carbapenems and are
not inhibited by clavulanic acid. They are assigned to class C according to the Ambler
classification. Expression of this type of β-lactamase is usually inducible, but in the case
Of E. coli it takes place constitutively at a very low level and does not confer β-lactam
resistance to wild strains [110]. Chromosomally encoded AmpC β-lactamases are identified
among E. coli strains from both humans [111] and animals [112].

In E. coli, mutations associated with an increase in resistance to fluoroquinolones are
most often observed in the protein GyrA and in ParC, in which a change in the encoded
amino acid alters the properties of the protein. The amino acids most often undergoing
substitution in GyrA in E. coli are Ser83 and Asp87 [113]. It should be noted that single
mutations in the gyrA gene can contribute to the resistance of bacterial strains to quinolones,
but in order for resistance to develop, additional mutations are required in gyrA and/or
parC. In clinical E. coli isolates 1–4 mutations have been detected in gyrA, gyrB and parC from
strains isolated from dogs and cats [114]. In addition, there are mechanisms of resistance to
fluoroquinolones which are encoded by plasmids—plasmid-mediated quinolone resistance
(PMQR). For plasmids carrying PMQR genes belong RCR, IncF, IncN, IncX1, IncX2. [105].
Clinically they are less important than mechanisms of mutation at the target site, i.e., gyrase
and topoisomerase. This group of mechanisms includes Qnr proteins changing the target
site of the antibiotic and structurally modifying fluoroquinolones and aminoglycosides, a
bifunctional variant of the enzyme aminoglycoside acetyltransferase—AAC(60 )-Ib-cr, and
efflux pump proteins associated with active transport—QepA and OqxAB [115]. These
determinants do not lead to a high level of resistance to quinolones/fluoroquinolones, only
reducing susceptibility to them. Nevertheless, they can increase resistance to this group of
antimicrobials by co-existing with mechanisms of resistance encoded chromosomally. All
these mechanisms of resistance to fluoroquinolones have been confirmed in E. coli isolated
from companion animals, livestock and humans [116,117].
Another mechanism of resistance, involving active removal of fluoroquinolone molecules
from the bacterial cell in order to reduce the concentration of the drug in the cytoplasm,
is complexes of transport proteins called efflux pumps [118]. In the case of E. coli, several
pump systems have been identified (AcrAB-TolC, EmrAB, MdfA, TehA, EmrE, AcrE, and
EmrD). The best understood are mechanisms associated with the presence of AcrAB-TolC
efflux pumps [119].

One cause of resistance to aminoglycosides is chromosomal mutations altering the
binding sites of the antibiotic and modification of 16S rRNA mediated by methylases.
Actinobacteria with the ability to produces aminoglycosides protect themselves against
their own aminoglycoside metabolites by producing 16S ribosomal RNA methyltransferase
(16S-RMTase), which prevents them from binding to 16S rRNA. Ten 16S-RMTases have
thus far been identified: ArmA, RmtA, RmtB, RmtC, RmtD, RmtE, RmtF, RmtG, RmtH
and NmpA [120]. In E. coli, genes coding for 16S-RMTase, armA, rmtB, rmtD, and rmtE
have been detected in strains from chickens, pigs and cattle [121,122]. Only one acquired
16S-RMTase—NpmA—has been detected in E. coli. This enzyme was identified in a clinical
human strain of E. coli in Japan in 2007 [123]. NpmA is responsible for resistance to
gentamicin, tobramycin, and amikacin, but also confers a broader spectrum of resistance
to this group of antibiotics, including neomycin and apramycin. It should be noted that
some genes encoding 16S-RMTases co-exist with other factors responsible for resistance
to antibiotics. An example is the high prevalence of the gene armA in Enterobacteriaceae
producing NDM (New Delhi metallo-β-lactamase) carbapenemase, which is also produced
Antibiotics 2022, 11, 1079 14 of 40
by E. coli. Studies of plasmids transferring blaNDM have shown that the gene often co-
exists with the armA gene or other 16S-RMTase genes (especially rmtB, rmtC and rmtF) on
the same plasmids [120]. Pulss et al. [124] identified an E. coli isolate from pigs which in
addition to armA contained other genes: blaCMY-2 , blaOXA-181 and mcr-1.
Another mechanism of resistance to aminoglycosides is enzymes modifying aminogly-
coside antibiotics. These can be divided into three groups depending on their mechanism
of action: acetyltransferases (AAC), which catalyse acetylation of the amine group of amino
sugars, nucleotidyltransferases (ANT), which attach nucleotide molecules from ATP to the
hydroxyl group of amino sugars located in the aminoglycoside molecule, and phosphotrans-
ferases (APH), responsible for phosphorylation of the hydroxyl group of the sugar residue
of the antibiotic. AAC, ANT and APH can be located on a plasmid, chromosome or inte-
gron. Several dozen AACs inducing resistance to aminoglycosides have been identified in
various genera of bacteria, many of which have been confirmed in E. coli. In the case of
E. coli strains from animals and humans, the most commonly identified are acetyltransferases
AAC(3)-II/IV and AAC(6)-Ib [125,126]. Among aminoglycoside phosphotransferases charac-
teristic of E. coli isolated from various animal species, the most common are APH(6)-Ia and
APH(6)-Id, encoded by strA and strB, respectively. Examples of nucleotidyltransferases found
for E. coli include ANT(2”) encoded by aadB and ANT(3”) encoded by aadA [127].

The mechanism of resistance to tetracyclines most often involves efflux pumps, tasked
with pumping the antibiotic out of the cytoplasm. Genes encoding efflux systems which
determine resistance to tetracyclines in E. coli include tet(A), tet(B), tet(C), tet(D), tet(E),
tet(G), tet(J), tet(L) and tet(Y). Another mechanism of resistance to tetracyclines is proteins
whose task is to protect the ribosome. By binding to ribosome they limit binding of
tetracyclines to it. In E. coli this group includes proteins encoded by two genes: tet(M) and
tet(W). In addition, the gene tet(X) has been identified for E. coli; it encodes oxidoreductase,
whose function is inactivation of first- and second-generation tetracyclines [128]. The
most commonly recorded genes encoding efflux systems are tet(A), tet(B) and indirectly
tet(C) [129,130]. It should be noted that in bacteria which have been tested for the presence
of tet genes, they have not always been identified singly. For example, Jahantigh et al. [131],
in addition to strains carrying a single tet gene mainly tet(A) and also tet(B), tet(C) and
tet(D), confirmed the presence of isolates carrying two or three tet genes simultaneously
(43.3% and 13.3%, respectively).
3.3.5. Resistance to Sulphonamides and Trimethoprim

Mechanisms determining resistance to sulphonamides mainly include the presence of
sul genes encoding dihydropteroate synthase with low affinity for sulphonamides, which
means that the bacteria replicate normally in an environment containing sulphonamides.
Currently four genes of resistance to sulphonamides (sul1, sul2, sul3 and sul4) have been
identified on plasmids [132]. IncFII and IncI1 are plasmids carrying genes encoding resis-
tance to suplhonamides [133]. Resistance to trimethoprim is determined by the presence of
the dfr gene encoding dihydrofolate reductases, which are not susceptible to this antimicro-
bial. The sul1 gene is located in the gene cassette in the variable part of class 1 integrons and
often co-exists with other resistance genes. Genes sul2 and sul3 are also located on plasmids
on which other determinants of resistance are present. The most commonly recorded genes
determining resistance to sulphonamides in E. coli are sul1 and sul2 [134,135].
The dfr genes determining resistance to trimethoprim have been identified many times
in various gram-negative bacteria, including E. coli. They have been divided into two
groups based on their size and structure: dfrA and dfrB. The dfrA genes encode proteins 152
to 189 amino acids in length, whereas proteins encoded by another group of genes—dfrB—
have only 78 amino acids. Both genes are located on gene cassettes, which are insIrted into
class I or II integrons [136]. In the case of E. coli, the vast majority of genes identified are
dfrA genes [137].
Antibiotics 2022, 11, 1079 15 of 40
3.3.6. Resistance to Phenicols

Due to the high toxicity and numerous side effects of nonfluorinated phenicols, chlo-
ramphenicol and its derivatives are no longer used in treatment of animals intended for
consumption. They are still used, however, in treatment of pets. The first mechanism
of bacterial resistance to chloramphenicol, which remains the most common, is enzy-
matic inactivation through acetylation of the drug by various types of chloramphenicol
acetyltransferases—CATs (the mechanism is manifested as the presence of the cat gene).
Chloramphenicol acetyltransferase modifies the antibiotic by transforming it into inactive
derivatives—monoacetates or diacetates. The chloramphenicol acetyltransferase gene is
usually encoded on a plasmid or transposon and can transpose to the chromosome [138].
Expression of the enzyme in the case of E. coli is encoded constitutively. Other mechanisms
of resistance include active efflux of nonfluorinated phenicols (presence of the gene cmlA)
or fluorinated and nonfluorinated phenicols (presence of the gene floR) from the bacterial
cell and the activity of rRNA methylase encoded by the gene cfr [139]. In E. coli isolated
from animals, CATs belonging to group A1 (catI gene), B2 (catB2 gene) and B3 (catB3 gene)
have been identified [140].
3.3.7. Resistance to Polymyxins

Polymyxins influence both the outer and cytoplasmic membrane of various species
of gram-negative bacteria, including Enterobacteriaceae, also acting on E. coli. One of the
mechanisms of resistance to polymyxins in E. coli strains is modification of lipid A of
LPS through the addition of phosphoethanolamine (PEtN) and/or 4-amino-4-deoxy-L-
arabinose (L-Ara4N), which decreases the affinity of colistin to the bacterial cell. This
chromosomal resistance mechanism to colistin in E. coli is the result of activation of two-
component systems PmrA/PmrB and PhoP/PhoQ by specific mutations of genes (pmrA,
pmrB, phoP, and phoQ) encoding proteins of these systems or environmental stimuli leading
to overexpression of genes modifying LPS [141]. The first gene of resistance to polymyxins
was identified in 2015, located on a plasmid from an E. coli strain from a pig. The gene
encoding phosphoethanolamine transferase MCR-1 was designated mcr-1 [142]. The fol-
lowing year a paper was published in which Xavier et al. [143] identified another gene
located on a plasmid, mcr-2, determining colistin resistance, with over 77% similarity to
mcr-1. Thus far several mcr genes and their variants have been isolated from E. coli strains
of animal origin [144,145].
E. coli isolates tested in various parts of the world, obtained from human, animals and
directly from the environment, have shown the highest resistance to amoxicillin (70.5–95%),
while the smallest percentage of strains have been resistant to colistin (0.8%). By far the
highest percentage of resistance to amoxicillin has been noted in strains isolated from
animals [146]. High resistance was also observed for cefotaxime (~60%), ceftazidime
(50–58%), tetracycline (50–55%) and ampicillin (45–50%). It should be noted that strains
from humans and animals have shown similar resistance to these antibiotics. E. coli
strains isolated from poultry in Poland have shown a high percentage of strains resistant
to ampicillin (100%), doxycycline (100%), ciprofloxacin and streptomycin (81.3%), and
amoxicillin/clavulanic acid (75%) [147].
The examples of the prevalence of antibiotic resistance gens in E. coli strains isolated
from the environment and different animal species has been presented in Table 2.
Antibiotics 2022, 11, 1079 16 of 40
Table 2. The examples of the prevalence of antibiotic resistance gens in E. coli strains isolated from the environment and different animal species.
Source of Isolation of the Strains and Percentage (%) of Positive Isolates Showing the Presence of Resistance Genes
Companion Environment
Antibiotic
Poultry, Animals (Cats, (Surface Soil, Sewage,
Resistance Genes Humans Ruminants Pigs Food References
Wild Birds Dogs, Horses, Drinking and
Pet Birds) Pond Water)
blaCTX-M 96.6 46.5 - 34.65–48.9 10.1 -
blaTEM 58.6 56.5–97.1 86 24–57.97 17–95.28 0.8–18 -
blaSHV - 16.0 21 27.5 16.55 1.2–2.0 -
blaOXA - - 5 - 7.09–14.02 - 15.5 Bahramian et al. [111];
Maynard et al. [148]; Sheikh et al. [130];
Beta-lactamases
blaCMY 72.4 88.4 - - 35.9–9.45 2.6–14.7 - Tian et al. [149]; Cormier et al. [150];
Gundran et al. [151]; Wang et al. [152];
blaDHA 20.7 - - -
Chen et al. [153]; Ilyas et al. [154];
blaACC 37.9 - - - - - - Ejikeugwu et al. [112];
Ombarak et al. [155];
blaIMP 72 16.7 - 10.2 - - - Mahmoud et al. [156];
Escherichia coli
blaVIM 28 - - 23.7 - - - Nowaczek et al. [135]
blaNDM 4–51.7 - - 31.8–19.8 2.36 - -

blaKPC 22.4 - - - - - 4.4
tet(A) 32.2 76.7–51.1 25–57.7 12.5–52.4 38.8–18 26.8–23.8 -
tet(B) 55.9 23.3–44.6 80–38.7 41.3 61.1–71 23.2–4.05 - Jahantigh et al. [131];
Maynard et al. [148];
Tetracyclines
tet(C) 7.2 5.4 25–5.1 1.7 - 4.3 - Belaynehe et al. [157];

tet(D) 1.3 - 2.9 0.8 - 0.4 - Ombarak et al. [155];
Schwaiger et al. [158];
tet(E) - - - - - - Gholami-Ahangaran et al. [159];
Ahmed et al. [137];
tet(G) 6.5 - - - - -
Nowaczek et al. [135]
tet(M) 6.6 2.9 - - - -
Antibiotics 2022, 11, 1079 17 of 40
Table 2. Cont.
Source of Isolation of the Strains and Percentage (%) of Positive Isolates Showing the Presence of Resistance Genes
Companion Environment
Antibiotic
Poultry, Animals (Cats, (Surface Soil, Sewage,
Resistance Genes Humans Ruminants Pigs Food References
Wild Birds Dogs, Horses, Drinking and
Pet Birds) Pond Water)
qnrA - - 2.0 - 17.32 - 0.4
qnrB 0.3 - - 1.3 93.70 - 1.1
qnrS 2.6 - 8.6 1.3 8.66 - 4.2 Chen et al. [117,153]
qepA 3.6 - 4.5 1.3 - - 2.6

oqxAB 5.2 - 51.0 19.8 20.2
aac(3)-IIa 70.7 80 - - 1 - -
aac(3)-IV 13.3 75 20 - 0.7
aac(6)-Ib 76.9 - - - - - -
rmtB - 5.3 2.6 - 0.9 - -
Quinolones
strA/B 61.2/63.8 76.7 52.6/54.7 - 2/3 18.4 28

aadA 59.2 71.7 - 20 1 4.95 10.4 Cirit et al. [125]; Maynard et al. [148];
Sheikh et al. [130]; Yu et al. [121];
aadB 3.1 - - - 1 - 0.5 Ombarak et al. [155];
aphA1 7.6 - 79 18.7 2 4.05 6.6 Abo-Amer et al. [160];
Schwaiger et al. [158];
aphA2 - - 19 - 1 - 1.7 Belaynehe et al. [161]; Usui et al. [162];
sulII 61.8 63.3 17.4–40.1 31.1–70.6 25.8 9.4–12.3 - Sigirci et al. [163]; Nowaczek et al. [135]
sulIII 3.3 - 7.6–2.2 - - 0.9–1.35 -

dhfrI - 76.3 20 - 40.3 - -
dhfrV - 15.8 47 - - - -
dhfrXIII - - 30 - - - -
dhfrIX - - - - 0.3 - -
Polymyxins
mcr-1 - 11.5 4.45–20.6 25.0 2.36 14.9 -

Khine et.al. [144]; Liu et al. [142];
mcr-2 - - 20.8 - - - - Wang et al. [152]; Chen et al. [153]
mcr-3 - - 0.43 - - - -
Maynard et al. [148];
catI 79 85.1–47.4 - 61.7 73.5 - -
Phenicoles
Belaynehe et al. [157];

Abo-Amer et al. [160];
floR 11.4 1.5–50 - - 9.7 - - Ibrahim et al. [164];
Derakhshandeh et al. [165];
cmlA - 10.4–18.4 - 72 4.8 - - Ahmed et al. [137]
Antibiotics 2022, 11, 1079 18 of 40
3.4. Listeria spp.

Bacteria of the genus Listeria are the aetiological agent of listeriosis in humans and
many animal species, including birds. The genus Listeria currently includes 17 species
present throughout the environment, among which the most commonly isolated is
L. monocytogenes, which is the third most common cause of death from food poison-
ing in human. Listeria ivanovii causes infections mainly in ruminants. Infections in hu-
mans caused by L. monocytogenes are especially common in risk groups such as pregnant
women, infants, the elderly, and human with reduced immunity [166]. Listeriosis in
human is usually treated with gentamicin in combination with and amoxicillin or ampi-
cillin. Other drugs of choice for pregnant women are erythromycin, vancomycin, and
trimethoprim/sulfamethoxazole [167].
Resistance of bacteria to antibiotics is associated with the presence of antibiotic resis-
tance genes especially in moving fragments. It was also described the transfer of plasmids
by conjugation with Enterococcus spp., Staphylococcus spp., Streptococcus spp. plasmids and
transposons carrying antibiotic resistance genes from these bacrogram specis to Listeria
and as well as between species of Listeria [168]. It has been shown that in Listeria spp., the
main mechanism responsible for the development of antibiotic resistance is the acquisition
of mobile genetic elements, e.g., self-transferable, mobilizable plasmids and conjugative
transposons [168]. Such mechanisms, referred to as efflux pumps, are significantly asso-
ciated with the occurrence of drug resistance in L. monocytogenes to fluoroquinolones,
macrolides and cefotaximes.

In the case of resistance to fluoroquinolones, there are three plasma-mediated mecha-
nisms of resistance (PMQR) as well as chromosomal resistance associated with mutations
causing modifications of amino acid sequences of individual subunits of topoisomerase II
and IV [169]:
• PMQR (plasmid-mediated quinolone resistance) mechanisms associated with the pres-
ence of Qrn proteins (Qrn A, B, S, and less often C and D), responsible for protecting
bacterial DNA and the enzymes gyrase and topoisomerase IV. The bifunctionality of
the variant of the enzyme aminoglycoside acetylotransferase (AAC60 )-lb-cr, through
modification of the aminoglycoside molecule, leads to the loss of affinity of subunit
16S rRNA to drugs such as tobramycin, kanamycin or amikacin;
• Active removal of fluoroquinolones from the interior of the cell by efflux pump proteins
QepA and OqxAB, e.g., through overexpression of the chromosomal genu lde, encoding
pump proteins;
• Point mutations in QRDRs (quinolone resistance-determining regions) in the genes
gyrA and gyrB encoding subunits of topoisomerase II (gyrase) or in the genes parC and
parE, responsible for encoding subunits of topoisomerase IV, the second main target
enzyme of fluoroquinolones besides topoisomerase II. It should be noted that both
enzymes play a major role during replication, transcription, recombination, and repair
of bacterial DNA.
PMQR mechanisms alone cause only a low level of resistance to fluoroquinolones, but
they promote selection of mutations in the gyrase and topoisomerase IV genes and acquisi-
tion of high-level resistance to fluoroquinolones by bacteria. Numerous reports indicate
that resistance to fluoroquinolones is a complex process resulting from the interaction of
several mechanisms determining multi-drug resistance in bacteria, e.g., PMQR together
with ESBL, pAmpC, and KPC and mutations in QRDRs in subunits of topoisomerase II
and IV [169].
3.4.2. Resistance to Macrolides

Macrolides antibacterial activity is with binding to the 50S ribosomal subunit which
inhibit the biosynthesis of 23S ribosomal RNA (rRNA). In Listeria spp., the resistance
against macrolides i.e., erythromycine is connected with the presence of two genes for
Antibiotics 2022, 11, 1079 19 of 40
resistance ermB and ermC. The erm (erythromycin ribosome methylase) genes encode
methyltransferases that modify 23S rRNA [170].

In the case of Listeria spp., thus far five determinants of resistance to tetracyclines have
been identified: tet(K), tet(L), tet(M), tet(S) and tet(T). The tet(M), tet(S) and tet(T) genes
are responsible for encoding specific cytoplasmic proteins protecting ribosomes against
antibiotics, while the tet(L) and tet(K) genes encode outer membrane proteins, responsible
for eliminating the antibiotic from the cell by active transport. Tetracycline resistance can be
transferred conjugatively between the different bacterial strains i.e., Enterococcus spp. and
Listeria spp. [171,172]. Resistance to a given antibiotic in different genera of bacteria may
also be linked to the occurrence of the same gene, e.g., in the case of resistance to tetracycline
and minocycline with the gene tet(M), which is the most common not only in Listeria but
also among other gram-positive bacteria of the genera Enterococcus, Staphylococcus and
Streptococcus, as well as some gram-negative bacteria [172]. The tet(M) has also been shown
to be linked to large integrative and conjugative elements (ICEs) with a broad range, e.g.,
Tn916 or Tn1545 [173].
3.5. Resistance to β-Lactams

An enzyme that determines resistance to beta-lactams as a result of hydrolysis in
Gram-positive bacteria (including Listeria spp.) Ferro B-lactamase, which may be located
on the chromosome, plasmids or genetic material of bacterial phages [174] The presence of
fosA, fosB, fosX genes has been confirmed in gram-negative (P. aeruginosa) and gram-positive
(S. aureus, L. monocytogenes) bacteria.
Extensive results of research on the occurrence of genes of resistance in strains of L.
monocytogenes isolated from humans and the environment were presented by Hanes and
Huang [175]. The authors showed a high prevalence of the genes fosX, lin, abc-f and tet(M)
as the four most commonly occurring genes in L. monocytogenes in Europe, Australia and
New Zealand, South America, South Africa and UK/Ireland. Examples of the prevalence
of genes of resistance in Listeria spp. isolated from various sources are presented in Table 3.
Some studies [176] have confirmed the occurrence of resistance to several groups
of antibiotics in Listeria spp. For example, L. monocytogenes strains isolated from more
than a dozen dairy cattle farms showed resistance to ampicillin (92%, MIC > or =2),
rifampicin (84%, MIC> or =4), rifamycin (84%, MIC> or =4), florfenicol (66%, MIC > or
=32), tetracycline (45%, MIC> or =16), penicillin G (40%, MIC> or =2) and chloramphenicol
(32%, MIC> or =32).
A study by Kayode et al. [177] carried out in the United States confirmed high re-
sistance to several groups of antimicrobials in L. monocytogenes strains isolated from the
natural environment, surface water (rivers), wastewater, and irrigation water. Strains
showed a high percentage of resistance to sulphonamides (sulfamethoxazole, STX) > 63.16%,
tetracycline (oxytetracycline) 54.39%; β-lactams (amoxicillin) 50.88%, penicillin G 40.35%;
aminoglycosides (streptomycin) 47.37%; cephalosporins (cefotetan) 45.61% and macrolides
(erythromycin) 43.85%. The values for phenicols (chloramphenicol) and vancomycin were
<40% (38.60% and 36.84%, respectively).
In the study Hailu et al. [178] the authors confirmed the 100% multi-resistance (MDR)
of L. monocytogenes isolates obtained from dairy and poultry farms, manure, and soil
in Ohio, USA to lincomycin (clindamycin), Rifamicines (ifampicin), cephalosporins (cef-
triaxone, cefoxitin), Penem (meropenem), macrolides (azithromycin) and trimethoprim
sulfamethoxazole, with 100% resistance for each antimicrobial class. A high resistsnce
among the tested strains was also observed to Aminoglycosides- streptomycin (98.5%),
Quinolones-nalidixic acid (95.5%), Fluoroquinolone—levofloxacin (91%) and penicillin-
ampicillin (89.5%). As wrote Authors all L. monocytogenes strains isolated from poultry
farms were resistant to kanamycine, nalidic acis and levofloxin, and more than 50% Listeria
strains obtained from dairy farms were resistant to the cited antibiotics [178].
Antibiotics 2022, 11, 1079 20 of 40
In the case of L. monocytogenes strains obtained from groundwater in agricultural

areas of South Africa, a very high percentage of strains were resistant to tetracycline (90%),
doxycycline (85%), cefotaxime (80%), penicillin (80%), chloramphenicol (70%), linezolid
(65%), erythromycin (60%) and trimethoprim/sulfamethoxazole (55%). It should be noted
that most of the isolates showed multi-drug resistance to at least one antibiotic of three
or more antimicrobial groups, and the MAR (multiple antibiotic resistance) indices of all
multi-drug resistant isolates were 0.2 [167]. Listeria spp. strains isolated from pigs and
from a slaughterhouse in Brazil showed a high rate of resistance to ceftazidime (100%),
clindamycin (50%), daptomycin (80–100%), and fluoroquinolones, including ciprofloxacin
(10–100%), as well as nitrofurantoin (50–57%) and oxacillin (20–50%) [179].
One of the latest studies, analysing drug resistance among 120 L. monocytogenes strains
isolated in Poland [180] from a total of 6000 samples from pigs, cattle, and poultry, con-
firmed resistance to cotrimoxazole (45.8%), meropenem (43.3%), erythromycin (40.0%),
penicillin (25.8%), and ampicillin (17.5%), with a high level of multi-drug resistance. In
Germany [181], among 259 L. monocytogenes strains isolated from food and processing
environments and samples from patients, as many as 145 strains revealed multidrug resis-
tance (resistance to ≥3 antibiotics). The strains mainly showed resistance to daptomycin
(100%), tigecycline (40%), tetracycline (23%), and to a lesser extent to ciprofloxacin (10%),
ceftriaxone (8%), trimethoprim/sulfamethoxazole (6.5%) and gentamicin (4.6%).
Table 3. Prevalence of specific genes of resistance to selected antibiotics in Listeria spp.
Source of Isolation of the Strains and Percentage (%) of Positive Isolates Showing the Presence of
Resistance Genes
Antibiotic Food
Resistance Poultry References
Products,
Genes Dairy Water Raw Farm and
Environment Dairy, Humans
Farms Environment Fish Slaugter-
Poultry
houses
and Pigs
Srinivasan et al. [176];
Beta-lactamases
penA 37 - 11.6 - - -
Jamali et al. [182];
ampC - 0 63 14 - 0 0 Haubert et al. [183];
Iwu & Okoh [167];
blaTEM - 10 75 - - - -
Kayode et al. [177];
Oswaldi et al. [184]
L. monocytogenes
blaz - 5 10 - - - -
tet(A) 32 0 85.2 23 - 35.7 0 Srinivasan et al. [176];

Tetracyclines
tet(B) 19 38 3.3 Iwu & Okoh, [167];

Oswaldi et al. [184];
tet(C) 17 63 25 7.86 72 Jamali et al. [182];
tet(M) - 4–18 70.37 25.6 52.6 14.3 70 Davanzo et al. [185];
Bae et al. [186];
tet(O) 8 8 Heidarzadeh et al. [187];
Hanes and Huang [175];
tet(S) 9.1 Hailu et al. [178]
Sulphonamides Quinolones
strA 34 9 0 - 0 -
Srinivasan et al. [176];
aadA 51.9 50 Hailu et al. [178];
aadB
dfrD 16 11 - - - - 27.3
sul1 16 3.33 38.24 0 0 0 13.6 Iwu & Okoh [167];
sul2 - 13.33 41.18 - - - -
Antibiotics 2022, 11, 1079 21 of 40
Table 3. Cont.
Source of Isolation of the Strains and Percentage (%) of Positive Isolates Showing the Presence of
Resistance Genes
Antibiotic Food
Resistance Poultry References
Products,
Genes Dairy Water Raw Farm and
Environment Dairy, Humans
Farms Environment Fish Slaugter-
Poultry
houses
and Pigs
Macrolides Lincosamides Aminoglicosides
ant6 18.2
aadA - 12.5 20 - - - -
strA - - 43.33 - - - - Oswaldi et al. [184];
Iwu & Okoh [167];
fosX 100 100 72–97
vgaD 100 13 100

Haubert et al. [183];
ermB - 42 - - 4 14.3 83.3 Davanzo et al. [185];
Heidarzadeh et al. [187];
Glicopeptides
vanA - 0 0 4.65 0 - - Jamali et al. [182];

Phenicoles
floR 66 4 0 - - - 0 Srinivasan et al. [176];

catI - - 53.3 - - - -
ermB—erythromycin; fosX—phosphomycin; vgaD—lincosamides, ant6—streptomycin; tet—tetracyclines, doxycy-
cline, tetracycline, and minocycline; (-)—not detected.
3.6. Salmonella spp.

Salmonella infections are a serious epidemiological and economic problem all over the
world in the context of food safety and public health. Salmonella bacteria also are among the
most common human foodborne pathogens in the European Union [188]. In 2014 in the EU
a total of 88,715 cases of salmonellosis were reported in humans, of which 34.4% involved
hospitalization [189]. Some serotypes also become localized in the reproductive tract.
In humans, infected with Salmonella the drug of choice is a third-generation cephalosporin,
e.g., ceptriaxone. After confirmation of complicated salmonella or typhoid infection,
fluoroquinolones (ciprofloxacin, ofloxacin or fleroxacin), azithromycin or ceftriaxone are
used. If treatment is not working as expected or if the isolated strains of Salmonella
are resistant to commonly used antibiotics, carbapenems (ertapen or meropen) may be
necessary. Patients with complicated infections usually require 7 to 10 days of antibiotics,
but typhoid fever usually takes 10–14 days of treatment. In carriers, treatment can last
up to four weeks (or longer), and fluoroquinolones are used for this purpose [190]. In
animals the using of Trimethoprim-sulfonamide combinations in Salmonella infections
shows a positive therapeutic effect. Alternatives for this treatment is using of ampicillin,
fluoroquinolones, or third-generation cephalosporins which should be continued daily for
up to 6 days [191].
Prevention and control of Salmonella infections in Western Europe and North America
is connected to the introduction of treatment of municipal water, pasteurization of dairy
products, and exclusion of human feces from food production. Because treatment of the
intestinal form of salmonellosis or asymptomatic infected individuas is a controversial issue
due to the risk of emergence of carriers of these bacteria or the development of Salmonella
resistance to the antibiotics used. Therefore, in EU countries, national programs for the
control of certain Salmonella spp. have been introduced, to control and reduce the level of
Antibiotics 2022, 11, 1079 22 of 40
infection in farm animals, especially poultry and pigs according to the Regulation of the
Minister of Agriculture and Rural Development [192]. The primary goal of such programs
is to prevent Salmonella infections in farm animals. Since salmonella are facultative
intracellular bacteria, the best protection is obtained with live attenuated vaccines which
used in pigs, cattle and chickens stimulate a strong cellular immune response and protect
the animals from both systemic infection and intestinal colonization. A live attenuated
vaccine containing the S. Choleraesuis serovar used in pigs appears to be effective in
reducing tissue colonization and protecting from disease following experimental infection
with virulent Salmonella strains under field conditions [193].
Also, in the case of developing countries, the strategies for enteric fever prevention
include improving sanitation, the safety of food and water supplies, identification and
treatment of chronic carriers of Salmonella ser. Typhi, and the use of typhoid vaccines. The
important treatment is also reduction of the proportion of people without access to drinking
water sources [190].
The most worrisome phenomenon is multidrug resistance, which limits the choice of
antimicrobials in treatment.
Mechanisms of resistance of Salmonella to antibiotics can be classified as modifications
of the action of an antimicrobial agent or its destruction, or active removal of the antibiotic
from the cell (efflux), a mechanism of medical importance. This system is expressed in
many clinically important bacteria. The genome of Salmonella enterica serovar Typhimurium
contains transport proteins AcrA and AcrB (with very high homology to proteins AcrA
and AcrB in Escherichia coli) and AcrD and Arf [194]. Transport of quinolone antibiotics,
tetracycline and chloramphenicol depends on protein AcrB [195].
Acquired resistance in Salmonella spp. may be caused by structural or regulatory
mutations in chromosomal genes and/or acquisition of new genetic sequences transported
onto mobile elements [196]. Both mechanisms of acquisition of genetic variation can cause
sudden changes in a population of bacteria and thus affect the evolution of resistance in
Salmonella spp. Following conjugation, mobile elements of DNA can be maintained as ex-
trachromosomal plasmids or can be completely or partially incorporated into the bacterial
chromosome and function as genomic islands [197]. The presence of one resistance mecha-
nism does not guarantee the survival of bacteria, so the simultaneous occurrence of several
different resistance mechanisms to different groups of antibiotics is common [198]. In the
case of Salmonella, resistance to aminoglycosides, β-lactam antibiotics, chloramphenicol,
quinolones, tetracyclines, sulphonamides, trimethoprim, and increasingly, colistin is the
most commonly observed.

Aminoglycosides are included among antibiotics active against gram-negative rods
and some strains of Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and
Mycobacterium tuberculosis [199]. The main mechanism of action involves disturbance of
translation by binding of the antibiotic to the bacterial 30S ribosomal subunit and/or bind-
ing to ribosomal proteins, resulting in the death of the cell. Resistance of Salmonella to
aminoglycosides is determined in part by enzymatic inactivation of the antibiotic through
chemical modification involving enzymes catalysing reactions such as acetylation, phospho-
rylation and adenylation [200]. Genes responsible for the production of aminoglycoside-
modifying enzymes are most often located on mobile genetic elements such as plasmids
and transposons, which allows them to spread between bacteria [201]. The most commonly
described gene determining the production of aminoglycoside-modifying enzymes is the
gene of resistance to tobramycin, kanamycin and amikacin aac(60 )-Ib [202].

Resistance to β-lactam antibiotics can also be determined by several mechanisms.
The first, occurring in both gram-positive and gram-negative bacteria, is associated with
penicillin-binding proteins (PBPs). The number of PBPs and their affinity for specific
Antibiotics 2022, 11, 1079 23 of 40
drugs differ between genera of bacteria, resulting in differences in the effectiveness of

β-lactams against specific microbes. B-lactam antibiotics form stable bonds with these
proteins and block their enzymatic activity, leading to disturbances in the structure of
peptidoglycan, followed by lysis of the bacterial cell. B-lactamases are encoded by genes
(blaTEM) located in the bacterial chromosome or on mobile genetic elements such as
plasmids, transposons or integrons. These mobile genes can be transferred between strains,
species or even genera of bacteria. There are two kinds of resistance mechanisms dependent
on PBPs. The first involves modification of natural PBPs so that they lose their affinity to
β-lactams, but at the same time serve as catalysts in cell wall production. The second type
involves acquisition of a foreign, complete gene encoding a PBP which does not react with
β-lactam molecules [203]. Two more resistance strategies consist in limiting the ability of a
β-lactam antibiotic to penetrate the bacterial cell. This involves reducing the number of
porin channels in the outer membrane of bacteria, thereby limiting the ability of β-lactam
molecules to enter the cell space. Another mechanism involves actively pumping the
drug out of the bacterial cell, which can be intensified by an increase in the expression
of efflux pump and porin systems, which are responsible for this process [204]. Another
mechanism involves production of β-lactamases, which are specific enzymes catalyzing
the hydrolysis of the β-lactam ring in the molecule of the drug [205]. Most gram-negative
rods have their own β-lactamases typical for a given species, whose genes are located in
chromosomal DNA. A second group of enzymes is extended-spectrum β-lactamases (ESBL),
which are mainly acquired, plasmid-encoded β-lactamases. Genes encoding ESBL are often
located on conjugative plasmids, including those with a broad host range, so that they are
rapidly spread, including between strains of different species. Bacterial strains capable
of ESBL synthesis are considered “alert pathogens”. Genetic analysis of bacterial strains
and resistance genes in farm animals, food, and humans has shown strong similarities and
common genetic traits, providing evidence that ESBL genes, mobile genetic elements and
resistant strains are transferred to humans via the food chain [206].
3.6.3. Resistance to Phenicols

Phenicols are broad-spectrum antibiotics whose mechanism of action involves re-
versible binding to the bacterial 30S ribosomal subunit and selective inhibition of the
activity of the enzyme peptidyl transferase, blocking biosynthesis of the protein in the
ribosomes [207]. Salmonella bacteria have two mechanisms of resistance to chloramphenicol.
The first involves enzymatic inactivation of the drug through acetylation by various types
of phosphotransferases and chloramphenicol acetyltransferase. The gene of resistance to
chloramphenicol is located in a plasmid. Other mechanisms of resistance of Salmonella to
chloramphenicol are active pumping of molecules of the antibiotic out of the bacterial cell
by transporter proteins (efflux pumps); changing the permeability of outer cell membranes;
and chromosome mutations which alter the protein of the 50S ribosomal subunit. S. Typhi
isolates have been shown to possess cat genes, which are transferred by a plasmid [208].
The presence of the cat1 and cat2 genes has also been detected in other Salmonella serovars,
such as Derby, Hadar, Enteritidis and Typhimurium [209]. The occurrence of other closely
related genes, cmlA and floR, which encode efflux pumps for chloramphenicol and flor-
fenicol, has also been described in Salmonella [210]. The presence of the gene floR has been
detected on genomic islands and in plasmids in various serovars of Salmonella: Agona,
Kiambu, Albany, Newport, Typhimurium, and Typhimurium var. Copenhagen [211,212].

Tetracyclines are broad-spectrum antibiotics which are effective against many gram-
positive and gram-negative bacteria, chlamydia, mycoplasmas, and even some protozoa.
They act mainly by stopping the binding of tRNA to the A site of the 30S ribosomal subunit
and inhibiting protein synthesis [213]. Resistance to tetracycline can be ascribed to a pump
removing the antibiotic from the interior of the bacterial cell. The most common tet genes
of resistance to tetracyclines belong to classes A, B, C, D and G [214] and are located both
Antibiotics 2022, 11, 1079 24 of 40
in plasmids and on the chromosome. Owing to their location in mobile genetic elements,
they are easily transferred between strains and are widespread among Salmonella bacteria.
Most genes are present in multi-drug resistant isolates, which makes them an important
marker in identification of potentially important Salmonella infections [215].
3.6.5. Resistance to Colistin

Resistance of Salmonella to colistin is encoded by mcr (mobile colistin resistance) genes,
which are located on mobile genetic elements in plasmid DNA and can be easily transferred
to other bacteria during cell division or horizontal gene transfer (conjugation or transduc-
tion). Five different mcr genes have thus far been described: mcr-1 to mcr-5 [216,217].
3.6.6. Resistance to Sulphonamides

Sulphonamides are a group of organic chemical compounds which are amides of
organosulphonic acids. They are bacteriostatic drugs whose mechanism of action involves
competitive inhibition of enzymes taking part in synthesis of tetrahydrofolic acid [213].
Resistance of Salmonella to sulphonamides has been ascribed to the presence of an additional
plasmid gene, sul, which determines expression of the inactive form of dihydropteroate
synthase (DHPS) [218]. Another gene coding for ‘normal’ (unmodified) DHPS is present
on the chromosome in both resistant and susceptible bacteria. Plasmid-encoded DHPSs are
1000 times less susceptible to sulphonamides than DHPSs encoded by a chromosomal gene.
Three genes have thus far been identified: sul1, sul2 and sul3. The gene sul1 is present in
many Salmonella serovars: Enteritidis, Hadar, Heidelberg, Orion, Rissen, Agona, Albany,
Derby, Djugu and Typhimurium [218]. Similarly, resistance to trimethoprim is mediated by
genes coding for variants of dihydrofolate reductase (dhfr and dfr) with reduced affinity for
the chemotherapeutic.
3.6.7. Resistance to Quinolones

Among Salmonella strains resistant to quinolones and/or fluoroquinolones, the most
commonly identified mechanism is the substitution of amino acids in quinolone resistance-
determining regions (QRDR) in genes gyrA and parC. However, plasmid-mediated quinolone
resistance genes (PMQR), i.e., the qnr genes (qnrA, qnrB, qnrC, qnrD, and qnrS), are increas-
ingly identified. Salmonella can acquire resistance by protecting the target site of the antibi-
otic, which can be an enzyme or a specific cell structure. For example, the plasmid-encoded
quinolone resistance protein (Qnr) confers resistance by acting as a DNA homologue, which
competes for binding of DNA gyrase and topoisomerase IV [219], making it more difficult
for the quinolone molecule to bind to DNA gyrase and thus protecting the bacteria against
the antibiotic. Salmonella can also modify the target site of the antibiotic to avoid binding.
For example, resistance to rifampicin is based on single-step point mutations, which cause
amino acid substitutions in the rpoB gene, reducing the drug’s affinity for DNA-dependent
RNA polymerase and allowing rpoB transcription to continue [9]. The widespread use of
fluoroquinolones in the poultry industry is a major problem. Quinolone-resistant bacteria
spreading through ingestion of contaminated food have been shown to affect treatment of
infections in human [189].
Analysis of resistance to antibiotics in Salmonella strains isolated from chicken eggs and
from samples collected from laying hens in North and South America, Africa, Europe and
Asia in 2013–2019 showed that the most commonly isolated serovars were S. Enteritidis
and S. Typhimurium. The high prevalence of S. Enteritidis in eggs and samples from
laying hens is likely due to the ability of this serovar to colonize tissues of the reproductive
system (ovary and oviduct) [220]. The highest percentages of strains (31.9–40.3%) exhibited
resistance to the β-lactam antibiotics ampicillin and amoxicillin/clavulanic acid and to
nalidixic acid (a fluoroquinolone). A much smaller percentage of strains were resistant
to aminoglycoside antibiotics: gentamicin (12.5%) and streptomycin (18%). Resistance to
ciprofloxacin (a fluoroquinolone) was 7.6%. No resistance to antibiotics commonly used in
human medicine was detected, i.e., ceftriaxone, cefotaxime, ceftazidime and cefepime, or
Antibiotics 2022, 11, 1079 25 of 40
to imipenem, meropenem and aztreonam, which according to the WHO are high priority
critically important. In addition, no strains were found to be resistant to chloramphenicol
or trimethoprim/sulfamethoxazole. In the case of trimethoprim/sulfamethoxazole, the
low level of resistance is probably due to the fact that sulphonamides are not widely used
in laying hens, in contrast to chicken broilers [221,222].
Strains of S. Enteritidis and S. Typhimurium obtained from broiler chickens in various
geographic regions showed a high level of resistance to nalidixic acid (80.3%), ampi-
cillin (64.8%), streptomycin (33%), amoxicillin/clavulanic acid (29.4%) and trimethoprim/
sulfamethoxazole (39.3%). Levels of resistance to ciprofloxacin (19%), chloramphenicol
(13.6%) and gentamicin (6%) were relatively low, most likely because gentamicin and chlo-
ramphenicol are no longer used to treat diseases in poultry [223–227]. Resistance of strains
isolated in European countries and the USA has generally been lower, which is linked
to the establishment of institutions and implementation of programmes for monitoring
antimicrobial agents in poultry production, i.e., the European Food Safety Authority and
the European Centre for Disease Prevention and Control, and the National Antibiotic
Resistance Monitoring System in the USA [228].
3.7. Staphylococcus spp.

Staphylococcus spp. is the most common in human and animal bacteria causing the
skin and mucosae clinical infections, such as pyoderma, otitis, soft tissue infection and
surgical wound in-fections including Staphylococcus aureus cased bacteremia (SAB) A fac-
tor increasing the importance of bacteria of the genus Staphylococcus in the pathology of
mammals and birds is their resistance to numerous antimicrobial agents [229]. Staphylo-
cocci are sensitive to penicillins, but due to the emergence of strains resistant to natural
penicillins, semi-synthetic penicillins such as oxacillin, nafcillin and cloxacillin are used
in therapies. Vancomycin is the second important antibiotic used as a basis especially for
fighting infections caused by methicillin resistant Staphylococcus spp. However, considering
the potential risk of resistance occurrence to vancmycin (there are already vancomycin-
resistant Staphylococcus strains in the world, also in Poland), the so-called alternative to
vancomycin, show good activity against resistant staphylococci including: trimethoprim-
sulfamethoxazole, ceftaroline, daptomycin, fosfomycin, linezolid, oritavancin/dalbavancin,
telavancin or omadacycline [230,231]. Vancomycin therapy has a specific risks especially
renal dysfunction, however, vancomycin is still the standard of the treatment of resistant
staphylococcal infections and is called also as the last chance antibiotic [229].
In animals, especially livestock, the therapy of infections caused by Staphylococcus spp.
is corelated with the kind of health problem. For example in North America in dairy
cows for the treatment of bovine mastitis are most often used cephapirin, pirlimycin and
ceftiofur [232]. In European Union countries the using of antibiotics usage for therapeutic
purposes is particularly high in pigs and poultry and less in cattle and sheep. In case of
skin infections in livestock, the most commonly used antimicrobial agents in livestock are
tetracyclines and penicillins. However, the veterinarian also use macrolides, aminoglyco-
sides and fluoroquinolones. For therapeutic purposes to treat bovine mastitis, pneumonia
in calves, metritis in cows and erysipelas in pigs β-lactams, especially penicillins, are most
often used [233,234].
Livestock have been identified as main reservoir of multi-drug resistance Staphylococcus
strains. Bacteria with this resistance profile have been classified as MDR (multi-drug
resistance), XDR (extensive drug resistance) and PDR (pandrug resistance). MDR refers to
strains that are not susceptible (with resistance or intermediate susceptibility) to at least
one antibiotic from at least three groups. XDR refers to bacteria that are non-susceptibility
to at least one agent in all but two or fewer antimicrobial categories. PDR indicates total
resistance to all antibiotics from all antimicrobial groups. Due to very high genetic and
phenotypic variation and to adaptation to the conditions of the environment, staphylococci
have become resistant to most currently used antimicrobials. [235].
Antibiotics 2022, 11, 1079 26 of 40

In the case of tetracyclines, one of the mechanisms of resistance of staphylococci
involves a decrease in their intracellular concentration due to a specific mechanism of
removal (efflux), associated with the presence of the genes tetK and tetL, encoding mem-
brane transporters [236]. Inducible resistance to tetracyclines is encoded by small plasmids,
whereas constitutive resistance is encoded by chromosomal determinants tet(M) and tet(O)
and is not associated with an efflux pump but only with active protection of the ribosome
against binding to tetracycline [237].
Active removal of the antibiotic from the cell is also a mechanism of resistance to
fluoroquinolones and the trimethoprim/sulfamethoxazole combination.

The main mechanisms of resistance to β-lactam antibiotics are the ability to produce
β-lactamase, resulting in resistance to natural penicillins, amino- and ureidopenicillins,
and production of penicillin-binding protein PBP2a, also called PBP20 , with low affinity
for β-lactam antibiotics, resulting in resistance to all β-lactam antibiotics currently used
in treatment [238]. The first epidemics induced by hospital-acquired methicillin-resistant
Staphylococcus aureus strains appeared in the late 1970s and early 1980s. These bacteria,
produce a modified penicillin-binding protein (PBP2a) to prevent β-lactam antibiotics
from binding to the target site of action, causing compounds whose structure contains a
β-lactam ring to become ineffective. Resistance to β-lactam antibiotics is determined by
the gene mecA or mecC, located in the chromosome and constituting part of the region
known as staphylococcal cassette chromosome mec (SCCmec). Both mecA and mecC are
responsible for synthesis of a modified protein that does not allow binding by penicillins,
cephalosporins (except for the latest generation, i.e., ceftaroline), carbapenems or monobac-
tams. A new homologue of mecA (mecALGA251), i.e., mecC, has been detected in bacteria
isolated from humans and farm animals in many European countries, as well as in pets
and wild animals. Cattle populations have been recognized as the main reservoir of mecC
strains [238]. Interestingly, the MECC gene has rarely been reported in bird species. It is
estimated that in in humans, about 80–90% of isolates associated with hospital-acquired
infections are methicillin-resistant coagulase-negative staphylococci (MRCNS). It has been
postulated that S. epidermidis may function as a reservoir of genes for the more pathogenic
species S. aureus. Moreover, results reported by other authors indicate that MRCNS are
isolated from food more often than methicillin-resistant S. aureus [239].
3.7.3. Resistance to Methicillin Macrolides Lincosamides and Streptogramin B

It should be noted that MLSB resistance in Staphylococcus spp. refers to resistance to
macrolides, lincosamides and streptogramin B. The mechanism of action of this group of
antibiotics involves inhibiting synthesis of proteins at the level of the 23S rRNA subunit,
where they bind to adenine at position 2058 or 2059 in domain V. The erm genes encode
ribosomal methylase modifying adenine at the target site of the antibiotics in the 23S rRNA
subunit, which blocks them from binding to the bacterial cell [240]. Many types of genes
of this group have been described in staphylococci: erm(A), erm(B), erm(C), erm(F), erm(G),
erm(Q), erm(T), erm(Y), erm(33), erm(43) and erm(48) [241]. There are two types of MLSB
resistance: constitutive and inducible. In the case of constitutive resistance, the bacteria
have active mRNA which enables methylase synthesis without an inductor. In induced
MLSB resistance, inactive mRNA is synthesized and is activated in the presence of an
inductor. Among MRSA strains derived from farm animals, the presence of more than
one erm gene has been described, most commonly erm(A) with erm(C) or erm(A) with
erm(B) [242,243].
Methicillin-resistant strains also usually have other resistance genes (e.g., determining
resistance to sulphonamides, gentamicin, kanamycin, streptomycin macrolides, fluoro-
quinolones or tetracyclines), so that they can be classified as MDR [244]. A widespread
mechanism of resistance to aminoglycosides among S. aureus is the synthesis of trans-
Antibiotics 2022, 11, 1079 27 of 40
ferases known as aminoglycoside-modifying enzymes (AME): acetyltransferase [(AAC

(60 )/APH(2”)] encoded by aac(60 )/aph(2”), phosphotransferase [APH(30 )-III, ANT (40 )-I
] encoded by aph (30 )-IIIa, ant(40 )-Ia; and nucleotidyltransferase [ANT (9)-I] encoded by
ant(6)-I [85,245]. The enzymes modify the antibiotic molecule and thereby deprive it of its
antimicrobial activity. Reduced susceptibility or resistance can also be due to disturbed
transport of aminoglycosides to the interior of the bacterial cell. Clinically the most com-
mon AMEs in staphylococci are ANT (40 )-I, AAC (60 )/APH(2”) and APH (30 )-III, which
modify aminoglycosides of therapeutic importance, including tobramycin, gentamicin and
kanamycin [246].

An important mechanism of resistance to fluoroquinolones in staphylococci is a muta-
tion of topoisomerase II (gyrase) and topoisomerase IV—bacterial enzymes involved in
replication of the target DNA for fluoroquinolones. Each of them contains two subunits,
gyr A and gyr B and par C and par E. Disturbance of synthesis of one enzyme or both
at the same time leads to inhibition of replication of the DNA of the cell and its death.
This region of mutation in the gyrase and topoisomerase genes is called the quinolone
resistance-determining region (QRDS). Mutation in the QRDS results in the replacement of
one amino acid with another at a specific active site of the enzyme [247].
Another mechanism is the acquisition of genes of drug resistance by importing them
from outside. This type of resistance is called plasmid resistance [248]. Due to the autonomy
of plasmids, they can be transferred to other bacterial cells without the involvement of
a chromosome. The co-occurrence of chromosomal and plasmid resistance means that
the drug resistance of bacteria to specific antimicrobials develops as a result of activation
of various mechanisms, depending on the drug. An important element of resistance of
S. aureus to fluoroquinolones is the presence of an efflux pump mechanism. In staphylo-
cocci, overexpression of proteins forming three efflux pump groups, Nor A, Nor B and
Nor C, causes a 4–8-fold increase in the MICs for fluoroquinolones. Transporter Nor
A is responsible for resistance to hydrophilic fluoroquinolones, such as norfloxacin and
ciprofloxacin, and Nor B and Nor C for resistance to fluoroquinolones, both hydrophilic
and hydrophobic, including moxifloxacin [249]. Resistance to moxifloxacin is only half
as high as resistance to ciprofloxacin, so it is particularly recommended in treatment of
Staphylococcus infections. Resistance to fluoroquinolones among hospital-acquired strains
of S. aureus is usually found together with methicillin resistance.
The gene cfr encodes methylase, with activity against adenine at position 2503 in do-
main V of 23S rRNA [250]. This is the target site of phenicols, lincosamides, oxazolidinones,
pleuromutilin and streptogramin. Methylation of the target site causes cross-resistance to
all of these antimicrobials. The cfr gene was first described in 2000 on plasmid pSCFS1
detected in a S. scuiri isolate from cattle [251]. It is located on plasmids which usually
additionally contain genes of the erm group, also determining multi-drug resistance [252].
Reports by the World Health Organization (WHO) indicate that the latest data on the
occurrence of various species of staphylococci in livestock and their resistance to antibiotics
differ depending on geographic location, animal species, and housing system, and are
also associated with the level of economic development of a given part of the world.
In comparison with northern Europe, there were generally more cases of resistance in
southern and south-eastern parts of the continent. In 2013–2016 the percentage share of
MRSA (methicillin-resistant S. aureus) significantly decreased in EU countries. Despite
this favourable trend, MRSA remains a priority issue for public health in Europe, as 10 of
30 countries have reported a MRSA percentage over 25% [253].
A study published in 2020 on the occurrence of Staphylococcus spp. In pigs in Greece
showed their presence in 48.61% of samples. The dominant species was S. aureus, while the
dominant coagulase-negative species were S. epidermidis and S. saprophyticus. These strains
showed high resistance to tetracycline (97.1%) and clindamycin (80.0%), but a much lower
percentage were resistant to fusidic acid (14.3%). No S. aureus strains resistant to methicillin
Antibiotics 2022, 11, 1079 28 of 40
(MRSA) or vancomycin were identified [254]. In a study on Staphylococcus in pigs in India,

the most commonly isolated species were S. sciuri, S. aureus, S. lentus and S. hyicus, with
most isolates showing multi-drug resistance. The highest percentage of strains showed
resistance to ampicillin and penicillin. There were also strains resistant to vancomycin, and
as many as 66.67% of S. aureus isolates were resistant to methicillin.
Transmission of drug-resistant strains from animals to humans usually takes place
through consumption of contaminated animal products (meat or eggs). Examination of
samples taken from chicken broilers during slaughter in Morocco showed that more than
half of isolated S. aureus strains (54%) were resistant to penicillin, 29.4% to tetracycline,
23.5% to erythromycin, and 17% to ciprofloxacin [255]. Most Staphylococcus spp. Isolates
obtained from hens from commercial flocks in Pakistan were resistant to the tetracycline
derivative tigecycline (74.8%), while among staphylococci isolated from backyard hens
the highest level of resistance was to clindamycin (72.1%). The presence of the mecA gene
was detected only in strains from backyard hens, whereas the genes ermC and tet(K) or
tet(M) were identified in Staphylococcus strains from both groups. Multi-drug resistance
was observed in 88% of strains. These results also reflect the influence of the environment
or habitat of birds in different rearing systems on the intestinal microbiota [256].
4. Conclusions
Acquisition of resistance to antibiotics by bacteria is one of the most important prob-
lems of modern medicine. A particularly disturbing phenomenon is the prevalence of very
high percentage, in many cases even 100% of multi-drug resistant foodborne pathogens in
developing countries, mainly in Africa and Asia. It has also been reported that, in many
bacterial species, the acquisition of drug resistance is mediated by the interspecies trans-
fer of resistance genes through the resistance mechanism. Such a transfer, among others
by plasmid transfer by conjugation confirmed in numerous studies in Enterococcus spp.,
Styaphylococcus spp., Streptococcus spp., Listeria spp. indicates a significant global risk of
continuous increase especially multi-drug resistance among bacteria.
Therefore, there is a need to monitor the resistance of these bacteria which will allow
you to control the extent of the spread of drug resistance among bacteria on the world. The
occurrence of a variety of bacterial species in farm animals and their resistance to antibiotics
differ depending on geographic location, the animal species, and housing system, and is
also associated with the level of economic development of a given part of the world
Such a quick and easy spread of multidrug resistance among bacteria is a global threat
to humans and animals and imposes an obligation not only in the field of comprehensive
diagnosis of drug resistance, but also in the implementation of methods of bacterial control
alternative to antibiotics. Therefore, there is a necessity to develop of novel strategies in
control of bacterial infectious is high demand. In response, several new therapies have
been tested with using of bacteriophages, antimicrobial peptides, and combinations of two
or more antibiotics in therapy.
However, due to the fact that most infections occur through the alimentary tract, it is
necessary to take preventive measures such as improving sanitation, ensuring the safety of
food and water supplies, rapid identification and treatment, and the development of new
generation vaccines to reduce the susceptibility to infection.
Supplementary Materials: The following supporting information can be downloaded at: https://
www.mdpi.com/article/10.3390/antibiotics11081079/s1, Table S1. The first or latest cases of antibiotic
resistance of chosen foodborne pathogens in different parts of the world. References [257–302] are
cited in the Supplementary Materials.
Author Contributions: Writing individual sections of the manuscript: R.U.-C.—the conception of
the manuscript, writing the section of Listeria spp., full editoring of the manuscript, A.M.—sections
of Salmonella spp., Staphylococcus spp., D.S.-P.—section of Enterococcus spp., K.W. and J.O.—section
of Campylobacter spp., A.N. and M.D.—section of E.coli. All authors have read and agreed to the
published version of the manuscript.
Antibiotics 2022, 11, 1079 29 of 40
Funding: This research received no external funding.

Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data is contained within this article and Supplementary Materials.
Conflicts of Interest: The authors declare that there is no conflict of interest.
References
1. Bengtsson-Palme, J.; Kristiansson, E.; Larsson, D.G.J. Environmental factors influencing the development and spread of antibiotic
resistance. FEMS Microbiol. Rev. 2018, 42, 68–80. [CrossRef] [PubMed]
2. Regulation (EU) 2019/6 of the European Parliament and of The Council of 11 December 2018 on Veterinary Medicinal Products
and Repealing Directive 2001/82/EC. Off. J. Eur. Union 2019, 4, 43–167. Available online: https://eur-lex.europa.eu/legal-
content/EN/TXT/PDF/?uri=CELEX:32019R0006&from=EN (accessed on 22 November 2021).
3. Ruvalcaba-Gómez, J.M.; Villagrán, Z.; Valdez-Alarcón, J.J.; Martínez-Núñez, M.; Gomez-Godínez, L.J.; Ruesga-Gutiérrez, E.;
Anaya-Esparza, L.M.; Arteaga-Garibay, R.I.; Villarruel-López, A. Non-Antibiotics Strategies to Control Salmonella Infection in
Poultry. Animals 2022, 12, 102. [CrossRef] [PubMed]
4. Mourenza, A.; Gil, J.A.; Mateos, L.M.; Letek, M. Alternative Anti-Infective Treatments to Traditional Antibiotherapy against
Staphylococcal Veterinary Pathogens. Antibiotics 2020, 9, 702. [CrossRef]
5. Irving, W.; Boswell, T.; Ala’Aldeen, D. Mikrobiologia Medyczna. Krótkie Wyklady; Wydawnictwo Naukowe PWN: Warszawa,
Poland, 2008; pp. 285–287.
6. Acar, J.; Röstel, B. Antimicrobial resistance: An overview. Rev. Sci. Tech. Off. Int. Epiz. 2001, 20, 797–810. [CrossRef]
7. Giedraitienė, A.; Vitkauskienė, A.; Naginienė, R.; Pavilonis, A. Antibiotic resistance mechanisms of clinically important bacteria.
Medicina 2011, 47, 137–146. [CrossRef]
8. van Hoek, A.H.; Mevius, D.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J. Acquired antibiotic resistance genes: An overview.
Front. Microbiol. 2011, 2, 203. [CrossRef]
9. Munita, J.M.; Arias, C.A. Mechanisms of antibiotic resistance. Microbiol. Spectr. 2016, 4, 1–37. [CrossRef]
10. Martinez, J.L. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens.
Front. Microbiol. 2011, 2, 265. [CrossRef]
11. Smillie, C.S.; Smith, M.B.; Friedman, J.; Cordero, O.X.; David, L.A.; Alm, E.J. Ecology drives a global network of gene exchange
connecting the human microbiome. Nature 2011, 480, 241–244. [CrossRef]
12. Jutkina, J.; Marathe, N.P.; Flach, C.F.; Larsson, D.G.J. Antibiotics and common antibacterial biocides stimulate horizontal transfer
of resistance at low concentrations. Sci. Total Environ. 2018, 616–617, 172–178. [CrossRef]
13. Zhang, Y.; Gu, A.Z.; He, M.; Li, D.; Chen, J. Subinhibitory concentrations of disinfectants promote the horizontal transfer of
multidrug resistance genes within and across genera. Environ. Sci. Technol. 2017, 51, 570–580.
14. Poirel, L.; Madec, J.Y.; Lupo, A.; Schink, A.K.; Kieffer, N.; Nordmann, P.; Schwarz, S. Antimicrobial Resistance in Escherichia coli.
Microbiol. Spectr. 2018, 6, 4. [CrossRef]
15. W˛egleński, P. Podstawowe Koncepcje Genetyczne i Wybrane Metody Analizy Genetycznej u Różnych Grup Organizmów. In
Genetyka Molekularna; PWN: Warszawa, Poland, 2008; ISBN 978-83-01-14744-0.
16. Kaakoush, N.O.; Castaño-Rodríguez, N.; Mitchell, H.M.; Man, S.M. Global Epidemiology of Campylobacter Infection. Clin.
Microbiol. Rev. 2015, 28, 687–719. [CrossRef]
17. Tresse, O.; Alvarez-Ordóñez, A.; Connerton, I.F. Editorial: About the Foodborne Pathogen Campylobacter. Front. Microbiol.
2017, 8, 1908. [CrossRef]
18. Humphrey, T.; O’Brien, S.; Madsen, M. Campylobacters as Zoonotic Pathogens: A Food Production Perspective. Intern. J. Food
Microbiol. 2007, 117, 237–257. [CrossRef]
19. Gras, L.M.; Smid, J.H.; Wagenaar, J.A.; De Boer, A.G.; Havelaar, A.H.; Friesema, I.; French, N.P.; Busani, L.; van Pelt, W.
Risk Factors for Campylobacteriosis of Chicken, Ruminant, and Environmental Origin: A Combined Case-control and Source
Attribution Analysis. PLoS ONE 2012, 7, e42599. [CrossRef]
20. An, J.U.; Ho, H.; Kim, J.; Kim, W.H.; Kim, J.; Lee, S.; Mun, S.H.; Guk, J.H.; Hong, S.; Cho, S. Dairy Cattle, a Potential Reservoir of
Human Campylobacteriosis: Epidemiological and Molecular Characterization of Campylobacter jejuni from Cattle Farms. Front.
Microbiol. 2018, 9, 3136. [CrossRef] [PubMed]
21. Ge, B.; Wang, F.; Sjölund-Karlsson, M.; McDermott, P.F. Antimicrobial Resistance in Campylobacter: Susceptibility Testing
Methods and Resistance Trends. J. Microbiol. Meth. 2013, 95, 57–67. [CrossRef]
22. Allos, B.M. Campylobacter jejuni Infections: Update on Emerging Issues and Trends. Clin. Infect. Dis. 2001, 32, 1201–1206.
23. Dai, L.; Sahin, O.; Grover, M.; Zhang, Q. New and alternative strategies for the prevention, control, and treatment of antibiotic-
resistant Campylobacter. Transl. Res. 2020, 223, 76–88. [CrossRef] [PubMed]
24. European Food Safety Authority (EFSA); European Centre for Disease Prevention and Control (ECDC). The European Union
summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2019–2020.
EFSA J. 2022, 20, 7209.
Antibiotics 2022, 11, 1079 30 of 40
25. Silva, J.; Leite, D.; Fernandes, M.; Mena, C.; Gibbs, P.A.; Teixeira, P. Campylobacter spp. as a foodborne pathogen: A review. Front.
Microbiol. 2011, 2, 200. [CrossRef] [PubMed]
26. Luangtongkum, T.; Jeon, B.; Han, J.; Plummer, P.; Logue, C.M.; Zhang, Q. Antibiotic resistance in Campylobacter: Emergence,
transmission and persistence. Future Microbiol. 2009, 4, 189–200. [CrossRef]
27. Iovine, N.M. Resistance mechanisms in Campylobacter jejuni. Virulence 2013, 4, 230–240. [CrossRef]
28. Tang, Y.; Fang, L.; Xu, C.; Zhang, Q. Antibiotic resistance trends and mechanisms in the foodborne pathogen, Campylobacter. Anim.
Health Res. Rev. 2017, 18, 87–98. [CrossRef]
29. Corcoran, D.; Quinn, T.; Cotter, L.; Fanning, S. An investigation of the molecular mechanisms contributing to high-level
erythromycin resistance in Campylobacter. Int. J. Antimicrob. Agents 2006, 27, 40–45. [CrossRef]
30. Florez-Cuadrado, D.; Ugarte-Ruiz, M.; Meric, G.; Quesada, A.; Porrero, M.C.; Pascoe, B.; Sáez-Llorente, J.L.; Orozco, G.L.;
Domínguez, L.; Sheppard, S.K. Genome comparison of erythromycin resistant Campylobacter from turkeys identifies hosts and
pathways for horizontal spread of erm(B) genes. Front. Microbiol. 2017, 8, 2240. [CrossRef]
31. Luo, N.; Pereira, S.; Sahin, O.; Lin, J.; Huang, S.; Michel, L.; Zhang, Q. Enhanced in vivo fitness of fluoroquinolone-resistant
Campylobacter jejuni in the absence of antibiotic selection pressure. Proc. Natl. Acad. Sci. USA 2005, 102, 541–546. [CrossRef]
32. Luo, N.; Sahin, O.; Lin, J.; Michel, L.O.; Zhang, Q. In vivo selection of Campylobacter isolates with high levels of fluoroquinolone
associated with gyrA mutations and the function of the CmeABC efflux pump. Antimicrob. Agents Chemother. 2003, 47, 390–394.
[CrossRef]
33. Payot, S.; Bolla, J.M.; Corcoran, D.; Fanning, S.; Mégraud, F.; Zhang, Q. Mechanisms of fluoroquinolone and macrolide resistance
in Campylobacter spp. Microbes Infect. 2006, 8, 1967–1971. [CrossRef] [PubMed]
34. Ge, B.L.; McDermott, P.F.; White, D.G.; Meng, J.H. Role of efflux pumps and topoisomerase mutations in fluoroquinolone
resistance in Campylobacter jejuni and Campylobacter coli. Antimicrob. Agents Chemother. 2005, 49, 3347–3354. [CrossRef] [PubMed]
35. Lin, J.; Michel, L.O.; Zhang, Q. CmeABC Functions as a Multidrug Efflux System in Campylobacter jejuni. Antimicrob. Agents
Chemother. 2002, 46, 2124–2131. [CrossRef] [PubMed]
36. Yao, H.; Zhao, W.; Jiao, D.; Schwarz, S.; Zhang, R.; Li, X.-S.; Du, X.-D. Global distribution, Dissemination and Overexpression of
Potent Multidrug Efflux Pump RE-CmeABC in Campylobacter jejuni. J. Antimicrob. Chemother. 2021, 76, 596–600. [CrossRef]
[PubMed]
37. Lin, J.; Yan, M.; Sahin, O.; Pereira, S.; Chang, Y.J.; Zhang, Q. Effect of macrolide usage on emergence of erythromycin-resistant
Campylobacter isolates in chickens. Antimicrob. Agents Chemother. 2007, 51, 1678–1686. [CrossRef] [PubMed]
38. Lehtopolku, M.; Kotilainen, P.; Haanperä-Heikkinen, M.; Nakari, U.M.; Hänninen, M.L.; Huovinen, P.; Siitonen, A.; Eerola,
E.; Jalava, J.; Hakanen, A.J. Ribosomal mutations as the main cause of macrolide resistance in Campylobacter jejuni and
Campylobacter coli. Antimicrob. Agents Chemother. 2011, 55, 5939–5941. [CrossRef] [PubMed]
39. Cagliero, C.; Mouline, C.; Cloeckaert, A.; Payot, S. Synergy between efflux pump CmeABC and modifications in ribosomal
proteins L4 and L22 in conferring macrolide resistance in Campylobacter jejuni and Campylobacter coli. Antimicrob. Agents Chemother.
2006, 50, 3893–3896. [CrossRef]
40. Leclercq, R. Mechanisms of resistance to macrolides and lincosamides: Nature of the resistance elements and their clinical
implications. Clin. Infect. Dis. 2002, 34, 482–492. [CrossRef]
41. Weisblum, B. Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 1995, 39, 577–585. [CrossRef]
42. Sharifi, S.; Bakhshi, B.; Najar-Peerayeh, S. Significant contribution of the CmeABC Efflux pump in high-level resistance to
ciprofloxacin and tetracycline in Campylobacter jejuni and Campylobacter coli clinical isolates. Ann. Clin. Microbiol. Antimicrob.
2021, 20, 36. [CrossRef]
43. Taylor, D.E.; Courvalin, P. Mechanisms of antibiotic resistance in Campylobacter species. Antimicrob. Agents Chemother. 1988, 32,
1107–1112. [CrossRef]
44. Pratt, A.; Korolik, V. Tetracycline resistance of Australian Campylobacter jejuni and Campylobacter coli isolates. J. Antimicrob.
Chemother. 2005, 55, 452–460. [CrossRef]
45. Pumbwe, L.; Randall, L.P.; Woodward, M.J.; Piddock, L.J. Evidence for multiple-antibiotic resistance in Campylobacter jejuni not
mediated by CmeB or CmeF. Antimicrob. Agents Chemother. 2005, 49, 1289–1293. [CrossRef]
46. Zeng, X.; Brown, S.; Gillespie, B.; Lin, J. A single nucleotide in the promoter region modulates the expression of the β-lactamase
OXA-61 in Campylobacter jejuni. J. Antimicrob. Chemother. 2014, 69, 1215–1223. [CrossRef]
47. Rivera-Mendoza, D.; Martínez-Flores, I.; Santamaría, R.I.; Lozano, L.; Bustamante, V.H.; Pérez-Morales, D. Genomic analysis
reveals the genetic determinants associated with antibiotic resistance in the zoonotic pathogen Campylobacter spp. Distributed
globally. Front. Microbiol. 2020, 11, 513070. [CrossRef]
48. Wieczorek, K.; Osek, J. A five-year study on prevalence and antimicrobial resistance of Campylobacter from poultry carcasses in
Poland. Food Microbiol. 2015, 49, 161–165. [CrossRef]
49. Meistere, I.; K, ibilds, J.; Eglı̄te, L.; Alksne, L.; Avsejenko, J.; Cibrovska, A.; Makarova, S.; Streikiša, M.; Grantin, a-Ievin, a, L.; Bērzin, š,
A. Campylobacter species prevalence, characterisation of antimicrobial resistance and analysis of whole-genome sequence of
isolates from livestock and humans, Latvia, 2008 to 2016. Euro Surveill. 2019, 24, 1800357. [CrossRef]
50. Tenhagen, B.A.; Flor, M.; Alt, K.; Knüver, M.T.; Buhler, C.; Käsbohrer, A.; Stingl, K. Association of antimicrobial resistance in
Campylobacter spp. In broilers and turkeys with antimicrobial use. Antibiotics 2021, 10, 673. [CrossRef]
Antibiotics 2022, 11, 1079 31 of 40
51. European Medicines Agency (EMA); European Surveillance of Veterinary Antimicrobial Consumption. Sales of Veterinary
Antimicrobial Agents in 31 European Countries in 2019 and 2020; EMA/58183/2021; European Medicines Agency: Amsterdam, The
Netherlands, 2021.
52. European Commission. Commission Implementing Decision of 17 November 2020 on the monitoring and reporting of antimicro-
bial resistance in zoonotic and commensal bacteria and repealing Implementing Decision 2013/652/EU, 2020/1729/EU. Off. J.
Eur. Union 2020, L387, 8–21.
53. Sangaré, L.; Nikiéma, A.K.; Zimmermann, S.; Sanou, I.; Congo-Ouédraogo, M.; Diabaté, A.; Diandé, S.; Guissou, P.I.
Campylobacter spp. Epidemiology and Antimicrobial Susceptibility in a Developing Country, Burkina Faso (West Africa). Afr. J.
Clin. Exp. Microbiol. 2012, 13, 110–117. [CrossRef]
54. Chala, G.; Eguale, T.; Abunna, F.; Asrat, D.; Stringer, A. Identification and Characterization of Campylobacter Species in Livestock,
Humans, and Water in Livestock Owning Households of Peri-urban Addis Ababa, Ethiopia: A One Health Approach. Front.
Public Health 2021, 9, 750551. [CrossRef]
55. Wieczorek, K.; Wołkowicz, T.; Osek, J. Antimicrobial resistance and virulence-associated traits of Campylobacter jejuni isolated
from poultry food chain and humans with diarrhea. Front. Microbiol. 2018, 9, 1508. [CrossRef]
56. Elhadidy, M.; Ali, M.M.; El-Shibiny, A.; Miller, W.G.; Elkhatib, W.F.; Botteldoorn, N.; Dierick, K. Antimicrobial resistance patterns
and molecular resistance markers of Campylobacter jejuni isolates from human diarrheal cases. PLoS ONE 2020, 15, e0227833.
[CrossRef]
57. Zhang, L.; Li, Y.; Shao, Y.; Hu, Y.; Lou, H.; Chen, X.; Wu, Y.; Mei, L.; Zhou, B.; Zhang, X.; et al. Molecular characterization and
antibiotic resistant profiles of Campylobacter species isolated from poultry and diarrheal patients in Southeastern China 2017–2019.
Front. Microbiol. 2020, 11, 1244. [CrossRef] [PubMed]
58. Wallace, R.L.; Bulach, D.; McLure, A.; Varrone, L.; Jennison, A.V.; Valcanis, M.; Smith, J.J.; Polkinghorne, B.G.; Glass, K.; Kirk,
M.D. Antimicrobial resistance of Campylobacter spp. Causing human infection in Australia: An international comparison. Microb.
Drug Resist. 2021, 27, 518–528. [CrossRef] [PubMed]
59. Schiaffino, F.; Colston, J.M.; Paredes-Olortegui, M.; François, R.; Pisanic, N.; Burga, R.; Peñataro-Yori, P.; Kosek, M.N. Antibiotic
resistance of Campylobacter species in a pediatric cohort study. Antimicrob. Agents Chemother. 2019, 63, e01911–e01918. [CrossRef]
[PubMed]
60. Tang, M.; Zhou, Q.; Zhang, X.; Zhou, S.; Zhang, J.; Tang, X.; Lu, J.; Gao, Y. Antibiotic Resistance Profiles and Molecular Mechanisms
of Campylobacter from Chicken and Pig in China. Front. Microbiol. 2020, 11, 592496. [CrossRef] [PubMed]
61. Béjaoui, A.; Gharbi, M.; Bitri, S.; Nasraoui, D.; Ben Aziza, W.; Ghedira, K.; Rfaik, M.; Marzougui, L.; Ghram, A.; Maaroufi, A.
Virulence Profiling, Multidrug Resistance and Molecular Mechanisms of Campylobacter Strains from Chicken Carcasses in Tunisia.
Antibiotics 2022, 11, 830. [CrossRef]
62. Nguyen, T.N.M.; Hotzel, H.; Njeru, J.; Mwituria, J.; El-Adawy, H.; Tomaso, H.; Neubauer, H.; Hafez, H.M. Antimicrobial
Resistance of Campylobacter Isolates from Small Scale and Backyard Chicken in Kenya. Gut Path. 2016, 8, 39. [CrossRef]
63. Andrzejewska, M.; Szczepańska, B.; Spica, D.; Klawe, J.J. Prevalence, virulence, and antimicrobial resistance of Campylobacter spp.
In raw milk, beef, and pork meat in northern Poland. Foods 2019, 8, 420. [CrossRef]
64. Bailey, M.A.; Taylor, R.M.; Brar, J.S.; Corkran, S.C.; Velásquez, C.; Novoa-Rama, E.; Oliver, H.F.; Singh, M. Prevalence and
antimicrobial resistance of Campylobacter from antibiotic-free broilers during organic and conventional processing. Poult. Sci.
2019, 98, 1447–1454. [CrossRef]
65. Leclercq, R. Enterococci acquire new kinds of resistance. Clin. Infect. Dis. 1997, 24 (Suppl. 1), S80–S84. [CrossRef]
66. Junior, J.C.; Fuchs, B.B.; Sabino, C.P.; Junqueira, J.C.; Jorge, A.O.C.; Ribeiro, M.S.; Gilmore, M.S.; Rice, L.B.; Tegos, G.P.; Hamblin,
M.R.; et al. Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect
Model. PLoS ONE 2013, 8, e55926. [CrossRef]
67. St˛epień-Pyśniak, D.; Hauschild, T.; Dec, M.; Marek, A.; Brzeski, M.; Kosikowska, U. Antimicrobial resistance and genetic diversity
of Enterococcus faecalis from yolk sac infections in broiler chicks. Poult. Sci. 2021, 100, 101491. [CrossRef]
68. O’Driscoll, T.; Crank, C.W. Vancomycin-resistant enterococcal infections: Epidemiology, clinical manifestations, and optimal
management. Infect. Drug. Resist. 2015, 8, 217–230.
69. St˛epień-Pyśniak, D.; Bertelloni, F.; Dec, M.; Cagnoli, G.; Pietras-Ożga, D.; Urban-Chmiel, R.; Ebani, V.V. Characterization and
comparison of Enterococcus spp. Isolates from feces of healthy dogs and urines of dogs with UTIs. Animals 2021, 11, 2845.
[CrossRef]
70. Ma, F.; Xu, S.; Tang, Z.; Li, Z.; Zhang, L. Use of antimicrobials in food animals and impact of transmission of antimicrobial
resistance on humans. Biosaf. Health 2021, 3, 32–38. [CrossRef]
71. Sifaoui, F.; Arthur, M.; Rice, L.; Gutmann, L. Role of penicillin-binding protein 5 in expression of ampicillin resistance and
peptidoglycan structure in Enterococcus faecium. Antimicrob. Agents Chemother. 2001, 45, 2594–2597. [CrossRef]
72. Ligozzi, M.; Pittaluga, F.; Fontana, R. Identification of a genetic element (psr) which negatively controls expression of Enterococcus
hirae penicillin-binding protein 5. J. Bacteriol. 1993, 175, 2046–2051. [CrossRef]
73. Murray, B.E. Vancomycin-resistant enterococcal infections. N. Engl. J. Med. 2000, 342, 710–721. [CrossRef]
74. Przybylski, M. Enterokoki oporne na wankomycyn˛e. II. Mechanizmy Oporności, epidemiologia. Post˛epy Mikrobiol. 2007, 46,
317–334.
75. Courvalin, P. Vancomycin resistance in gram-positive cocci. Clin. Infect. Dis. 2006, 42 (Suppl. 1), S25–S34. [CrossRef] [PubMed]
Antibiotics 2022, 11, 1079 32 of 40
76. Boyd, D.A.; Willey, B.M.; Fawcett, D.; Gillani, N.; Mulvey, M.R. Molecular characterization of Enterococcus faecalis N06-0364
with low-level ancomycin resistance harboring a novel Dala-D-Ser gene cluster, vanL. Antimicrob. Agents Chemother. 2008, 52,
2667–26672. [CrossRef] [PubMed]
77. Courvalin, P. Genetics of glycopeptide resistance in Gram-positive pathogens. Int. J. Med. Microbiol. 2005, 294, 479–486. [CrossRef]
[PubMed]
78. Kawalec, M.; Kedzierska, J.; Gajda, A.; Sadowy, E.; Wegrzyn, J.; Naser, S.; Skotnicki, A.B.; Gniadkowski, M.; Hryniewicz, W.
Hospital outbreak of vancomycin-resistant enterococci caused by a single clone of Enterococcus raffinosus and several clones of
Enterococcus faecium. Clin. Microbiol. Infect. 2007, 13, 893–901. [CrossRef] [PubMed]
79. Leclercq, R.; Dutka-Malen, S.; Brisson-Noël, A.; Molinas, C.; Derlot, E.; Arthur, M.; Duval, J.; Courvalin, P. Resistance of enterococci
to aminoglycosides and glycopeptides. Clin. Infect. Dis. 1992, 15, 495–501. [CrossRef] [PubMed]
80. Werner, G.; Coque, T.M.; Hammerum, A.M.; Hope, R.; Hryniewicz, W.; Johnson, A.; Klare, I.; Kristinsson, K.G.; Leclercq, R.;
Lester, C.H.; et al. Emergence and spread of vancomycin resistance among enterococci in Europe. Euro Surveill. 2008, 20, 19046.
[CrossRef]
81. Navarro, F.; Courvalin, P. Analysis of genes encoding d-alanine-d-alanine ligase-related enzymes in Enterococcus casseliflavus
and Enterococcus flavescens. Antimicrob. Agents Chemother. 1994, 38, 1788–1793. [CrossRef]
82. Depardieu, F.; Reynolds, P.E.; Courvalin, P. VanD-type vancomycin-resistant Enterococcus faecium 10/96A. Antimicrob. Agents
83. Patino, A.L.; Courvalin, P.; Perichon, B. vanE gene cluster of vancomycin–resistant Enterococcus faecalis BM4405. J. Bacteriol.
2002, 184, 6457–6464. [CrossRef]
84. McKessar, S.J.; Berry, A.M.; Bell, J.M.; Turnidge, J.D.; Paton, J.C. Genetic characterization of vanG, a novel vancomycin resistance
locus of Enterococcus faecalis. Antimicrob. Agents Chemother. 2000, 44, 3224–3228. [CrossRef]
85. Ramirez, M.S.; Tolmasky, M.E. Aminoglycoside modifying enzymes. Drug Resist. Updates 2010, 13, 151–171. [CrossRef]
86. Chow, J.W. Aminoglicoside resistance in enterococci. Clin. Infect. Dis. 2000, 31, 586–589. [CrossRef]
87. EUCAST 2019. Available online: www.escmid.org/research_projects/eucast/ (accessed on 1 January 2020).
88. Bentorcha, F.; De Cespédès, G.; Horaud, T. Tetracycline resistance heterogeneity in Enterococcus faecium. Antimicrob. Agents
89. Roberts, M.C. Update on macrolide-lincosamide- streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol.
Lett. 2008, 282, 147–159. [CrossRef]
90. Singh, K.V.; Weinstock, G.M.; Murray, B.E. An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this
species to clindamycin and quinupristin-dalfopristin. Antimicrob. Agents Chemother. 2002, 46, 1845–1850. [CrossRef]
91. Chenoweth, C.E.; Robinson, K.A.; Schaberg, D.R. Efficacy of ampicillin versus trimethoprim-sulfamethoxazole in a mouse model
of lethal enterococcal peritonitis. Antimicrob. Agents Chemother. 1990, 34, 1800–1802. [CrossRef]
92. Jacoby, G.A. Mechanisms of resistance to quinolones. Clin. Infect. Dis. Soc. Am. 2005, 41 (Suppl. 2), S120–S126. [CrossRef]
93. St˛epień-Pyśniak, D.; Hauschild, T.; Nowaczek, A.; Marek, A.; Dec, M. Wild birds as a potential source of known and novel
multilocus sequence types of antibiotic-resistant Enterococcus faecalis. J. Wild. Dis. 2018, 54, 219–228. [CrossRef]
94. Gawryszewska, I.; Malinowska, K.; Kuch, A.; Chrobak-Chmiel, D.; Trokenheim, L.L.; Hryniewicz, W.; Sadowy, E. Distribution of
antimicrobial resistance determinants, virulence-associated factors and clustered regularly interspaced palindromic repeats loci
in isolates of Enterococcus faecalis from various settings and genetic lineages. Pathog. Dis. 2017, 75, ftx021. [CrossRef]
95. Boccella, M.; Santella, B.; Pagliano, P.; De Filippis, A.; Casolaro, V.; Galdiero, M.; Borrelli, A.; Capunzo, M.; Boccia, G.; Franci, G.
Prevalence and Antimicrobial Resistance of Enterococcus Species: A Retrospective Cohort Study in Italy. Antibiotics 2021, 10, 1552.
[CrossRef]
96. Kotłowski, R.; Grecka, K.; Kot, B.; Szweda, P. New Approaches for Escherichia coli Genotyping. Pathogens 2020, 9, 73. [CrossRef]
97. Lindstedt, B.A.; Finton, M.D.; Porcellato, D.; Brandal, L.T. High frequency of hybrid Escherichia coli strains with combined
Intestinal Pathogenic Escherichia coli (IPEC) and Extraintestinal Pathogenic Escherichia coli (ExPEC) virulence factors isolated
from human faecal samples. BMC Infect Dis. 2018, 18, 544. [CrossRef]
98. Wasiński, B. Extra-intestinal pathogenic Escherichia coli—Threat connected with food-borne infections. Ann. Agric. Environ. Med.
2019, 26, 532–537. [CrossRef]
99. Shinozuka, Y.; Kawai, K.; Takeda, A.; Yamada, M.; Kayasaki, F.; Kondo, N.; Ssaki, Y.; Kanai, N.; Mukai, T.; Sawaguchi, M.; et al.
Influence of oxytetracycline susceptibility as a first-line antibiotic on the clinical outcome in dairy cattle with acute Escherichia
colied.stis. J. Vet. Med. Sci. 2019, 81, 863–868. [CrossRef]
100. Temmerman, R.; Pelligand, L.; Schelstraete, W.; Antonissen, G.; Garmyn, A.; Devreese, M. Enrofloxacin Dose Optimization for the
Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model. Antibiotics 2021, 10, 604.
[CrossRef]
101. Burow, E.; Rostalski, A.; Harlizius, J.; Gangl, A.; Simoneit, C.; Grobbel, M.; Kollas, C.; Tenhagen, B.A.; Käsbohrer, A. Antibiotic
resistance in Escherichia coli from pigs from birth to slaughter and its association with antibiotic treated. Prev. Vet. Med. 2019, 165,
52–62. [CrossRef]
102. Available online: https://ekolabos.pl/mechanizmy-opornosci-gram-ujemnych-paleczek-na-antibiotyki/ (accessed on 1
January 2021).
Antibiotics 2022, 11, 1079 33 of 40
103. Kong, K.F.; Schneper, L.; Mathee, K. B-lactam antibiotics: From antibiosis to resistance and bacteriology. APMIS Acta Pathol.
Microbiol. Immunol. Scand. 2010, 118, 1–36. [CrossRef]
104. Canton, R.; Novais, A.; Valverde, A.; Machado, E.; Peixe, L.; Baquero, F.; Coque, T.M. Prevalence and spread of extender spectrum
β-lactamase-producing Enterobacteriaceae in Europe. Clin. Microbiol. Infect. 2008, 14 (Suppl. 1), 144–153. [CrossRef]
105. Carattoli, A. Plasmids and the spread of resistance. Int. J. Med. Microbiol. 2013, 303, 298–304. [CrossRef]
106. Bush, K.; Jacoby, G.A. Updated functional classification of β-lactamases. Antimicrob. Agents Chemother. 2010, 54, 969–976.
[CrossRef] [PubMed]
107. Paterson, D.L.; Bonomo, R.A. Extended-spectrum β-lactamases: A clinical update. Clin. Microbiol. Rev. 2005, 18, 657–686.
[CrossRef]
108. Ejaz, H.; Younas, S.; Abosalif, K.; Junaid, K.; Alzahrani, B.; Alsrhani, A.; Abdalla, A.E.; Ullah, M.I.; Qamar, M.U.; Hamam, S.
Molecular analysis of blaSHV, blaTEM, and blaCTX-M in extended-spectrum -lactamase producing Enterobacteriaceae recovered
from fecal specimens of animals. PLoS ONE 2021, 16, e0245126. [CrossRef]
109. Jacoby, G.A. AmpC β-lactamases. Clin. Microbiol. Rev. 2009, 22, 161–182. [CrossRef] [PubMed]
110. Livermore, D.M. β-Lactamases in laboratory and clinical resistance. Clin. Microbiol. Rev. 1995, 8, 557–584. [CrossRef]
111. Bahramian, A.; Khoshnood, S.; Hashemi, N.; Moradi, M.; Karimi-Yazdi, M.; Jalallou, N.; Saki, M. Identification of metallo–
lactamases and AmpC production among Escherichia coli strains isolated from hemodialysis patients with urinary tract infection.
Mol. Biol. Rep. 2021, 48, 7883–7892. [CrossRef] [PubMed]
112. Ejikeugwu, C.; Esimone, C.; Iroha, I.; Igwe, D.O.; Ugwu, M.; Ezeador, C.; Duru, C.; Adikwu, M. Molecular Identification of MBL
Genes blaIMP-1 and blaVIM-1 in Escherichia coli Strains Isolated from Abattoir by Multiplex PCR Technique. Res. J. Microbiol.
2017, 12, 266–273.
113. Barnard, F.M.; Maxwell, A. Interaction between DNA gyrase and quinolones: Effects of alanine mutations at GyrA subunit
residues Ser(83) and Asp(87). Antimicrob. Agents Chemother. 2001, 45, 1994–2000. [CrossRef]
114. de Jong, A.; Muggeo, A.; El Garch, F.; Moyaert, H.; de Champs, C.; Guillard, T. Characterization of quinolone resistance
mechanisms in Enterobacteriaceae isolated from companion animals in Europe (ComPath II study). Vet. Microbiol. 2018, 216,
159–167. [CrossRef]
115. Strahilevitz, J.; Jacoby, G.A.; Hooper, D.C.; Robicsek, A. Plasmid-mediated quinolone resistance: A multifaceted threat. Clin.
Microbiol. Rev. 2009, 22, 664–689. [CrossRef]
116. Pereira, R.V.; Foditsch, C.; Siler, J.D.; Dulièpre, S.C.; Altier, C.; Garzon, A.; Warnick, L.D. Genotypic antimicrobial resistance
characterization of E. coli from dairy calves at high risk of respiratory disease administered enrofloxacin or tulathromycin. Sci.
Rep. 2020, 10, 19327. [CrossRef]
117. Chen, X.; Zhang, W.; Pan, W.; Yin, J.; Pan, Z.; Gao, S.; Jiao, X. Prevalence of qnr, aac(60 )-Ib-cr, qepA, and oqxAB in Escherichia coli
isolates from humans, animals, and the environment. Antimicrob. Agents Chemother. 2012, 56, 3423–3427. [CrossRef]
118. Hooper, D.C. Efflux pumps and nosocomial antibiotic resistance: A primer for hospital epidemiologists. Clin. Infect. Dis. 2005, 40,
1811–1817.
119. Sulavik, M.C.; Houseweart, C.; Cramer, C.; Jiwani, N.; Murgolo, N.; Greene, J.; Di Domenico, B.; Shaw, K.J.; Miller, G.H.;
Hare, R.; et al. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob.
Agents Chemother. 2001, 45, 1126–1136. [CrossRef]
120. Doi, Y.; Wachino, J.I.; Arakawa, Y. Aminoglycoside Resistance: The Emergence of Acquired 16S Ribosomal RNA Methyltrans-
ferases. Infect. Dis. Clin. N. Am. 2016, 30, 523–537. [CrossRef]
121. Yu, T.; He, T.; Yao, H.; Zhang, J.B.; Li, X.N.; Zhang, R.M.; Wang, G.Q. Prevalence of 16S rRNA Methylase Gene rmtB Among
Escherichia coli Isolated from Bovine Mastitis in Ningxia, China. Foodborne Pathog. Dis. 2015, 12, 770–777. [CrossRef]
122. Xia, J.; Sun, J.; Li, L.; Fang, L.X.; Deng, H.; Yang, R.S.; Li, X.P.; Liao, X.P.; Liu, Y.H. First Report of the IncI1/ST898 Conjugative
Plasmid Carrying rmtE2 16S rRNA Methyltransferase Gene in Escherichia coli. Antimicrob. Agents Chemother. 2015, 59, 7921–7922.
[CrossRef]
123. Wachino, J.; Shibayama, K.; Kurokawa, H.; Kimura, K.; Yamane, K.; Suzuki, S.; Shibata, N.; Ike, Y.; Arakawa, Y. Novel
plasmid-mediated 16S rRNA m1A1408 methyltransfrase, NpmA, found in a clinically isolated Escherichia coli strain resistant to
structurally diverse aminoglycosides. Antimicrob. Agents Chemother. 2007, 51, 4401–4409. [CrossRef]
124. Pulss, S.; Semmler, T.; Prenger-Berninghoff, E.; Bauerfeind, R.; Ewers, C. First report of an Escherichia coli strain from swine
carrying an OXA-181 carbapenemase and the colistin resistance determinant MCR-1. Int. J. Antimicrob. Agents 2017, 50, 232–236.
[CrossRef]
125. Cirit, O.S.; Fernández-Martínez, M.; Yayla, B.; Martínez-Martínez, L. Aminoglycoside resistance determinants in multiresistant
Escherichia coli and Klebsiella pneumoniae clinical isolates from Turkish and Syrian patients. Acta Microbiol. Immunol. Hung. 2019,
66, 327–335. [CrossRef]
126. Haldorsen, B.C.; Simonsen, G.S.; Sundsfjord, A.; Samuelsen, O. Norwegian Study Group on Aminoglycoside Resistance. Increased
prevalence of aminoglycoside resistance in clinical isolates of Escherichia coli and Klebsiella spp. In Norway is associated with
the acquisition of AAC(3)-II and AAC(60 )-Ib. Diagn. Microbiol. Infect. Dis. 2014, 78, 66–69. [CrossRef] [PubMed]
127. Marchant, M.; Vinué, L.; Torres, C.; Moreno, M.A. Change of integrons over time in Escherichia coli isolates recovered from
healthy pigs and chickens. Vet. Microbiol. 2013, 163, 124–132. [CrossRef] [PubMed]
128. Roberts, M.C. Update on acquired tetracycline resistance genes. FEMS Microbiol. Lett. 2005, 245, 195–203. [CrossRef] [PubMed]
Antibiotics 2022, 11, 1079 34 of 40
129. Seifi, S.; Khoshbakht, R. Prevalence of tetracycline resistance determinants in broiler isolated Escherichia coli in Iran. Br. Poult. Sci.
2016, 57, 729–733. [CrossRef]
130. Sheikh, A.A.; Checkley, S.; Avery, B.; Chalmers, G.; Bohaychuk, V.; Boerlin, P.; Reid-Smith, R.; Aslam, M. Antimicrobial resistance
and resistance genes in Escherichia coli isolated from retail meat purchased in Alberta, Canada. Foodborne Pathog. Dis. 2012, 9,
131. Jahantigh, M.; Samadi, K.; Dizaji, R.E.; Salari, S. Antimicrobial resistance and prevalence of tetracycline resistance genes in
Escherichia coli isolated from lesions of colibacillosis in broiler chickens in Sistan, Iran. BMC Vet. Res. 2020, 16, 267. [CrossRef]
132. Li, Q.; Li, Z.; Wang, Y.; Chen, Y.; Sun, J.; Yang, Y.; Si, H. Antimicrobial Resistance and Transconjugants Characteristics of sul3
Positive Escherichia coli Isolated from Animals in Nanning, Guangxi Province. Animals 2022, 12, 976. [CrossRef]
133. Wu, S.; Dalsgaard, A.; Hammerum, A.M.; Porsbo, L.J.; Jensen, L.B. Prevalence and characterization of plasmids carrying
sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human. Acta Vet. Scand. 2010, 52, 47. [CrossRef]
134. Jiang, H.; Cheng, H.; Liang, Y.; Yu, S.; Yu, T.; Fang, J.; Zhu, C. Diverse Mobile Genetic Elements and Conjugal Transferability
of Sulfonamide Resistance Genes (sul1, sul2, and sul3) in Escherichia coli Isolates From Penaeus vannamei and Pork From Large
Markets in Zhejiang, China. Front. Microbiol. 2019, 10, 1787. [CrossRef]
135. Nowaczek, A.; Dec, M.; St˛epień-Pyśniak, D.; Urban-Chmiel, R.; Marek, A.; Różański, P. Antibiotic Resistance and Virulence
Profiles of Escherichia coli Strains Isolated from Wild Birds in Poland. Pathogens 2021, 10, 1059. [CrossRef]
136. Faridah, H.D.; Dewi, E.K.; Effendi, M.H.; Plumeriastuti, H. A Review of Antimicrobial Resistance (AMR) of Escherichia coli on
Livestock and Animal Products: Public Health Importance. Sys. Rev. Pharm. 2020, 11, 1210–1218.
137. Ahmed, M.O.; Clegg, P.D.; Williams, N.J.; Baptiste, K.E.; Bennett, M. Antimicrobial resistance in equine faecal Escherichia coli
isolates from North West England. Ann. Clin. Microbiol. Antimicrob. 2010, 9, 12. [CrossRef]
138. Denis, O.; Rodriguez-Villalobos, H.; Struelens, M.J. CHAPTER 3—The problem of resistance. In Antibiotic and Chemotherapy,
9th ed.; Finch, R.G., Greenwood, D., Norrby, S.R., Whitley, R.J., Eds.; W.B. Saunders: London, UK, 2010; pp. 24–48, ISBN
978-0-7020-064-1.
139. Schwarz, S.; Kehrenberg, C.; Doublet, B.; Cloeckaert, A. Molecular basis of bacterial resistance to chloramphenicol and florfenicol.
FEMS Microbiol. Rev. 2004, 28, 519–542. [CrossRef]
140. Shaheen, B.W.; Oyarzabal, O.A.; Boothe, D.M. The role of class 1 and 2 integrons in mediating antimicrobial resistance among
canine and feline clinical E. coli isolates from the US. Vet. Microbiol. 2010, 144, 363–370. [CrossRef]
141. Rhouma, M.; Beaudry, F.; Thériault, W.; Letellier, A. Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action,
Microbial Resistance Emergence, and One Health Perspectives. Front. Microbiol. 2016, 7, 1789. [CrossRef]
142. Liu, Y.Y.; Wang, Y.; Walsh, T.R.; Yi, L.X.; Zhang, R.; Spencer, J.; Doi, Y.; Tian, G.; Dong, B.; Huang, X.; et al. Emergence of
plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular
biological study. Lancet Infect. Dis. 2016, 16, 161–168. [CrossRef]
143. Xavier, B.B.; Lammens, C.; Ruhal, R.; Kumar-Singh, S.; Butaye, P.; Goossens, H.; Malhotra-Kumar, S. Identification of a novel
plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Eurosurveillance 2016, 21, 30280.
[CrossRef]
144. Khine, N.O.; Lugsomya, K.; Kaewgun, B.; Honhanrob, L.; Pairojrit, P.; Jermprasert, S.; Prapasarakul, N. Multidrug Resistance and
Virulence Factors of Escherichia coli Harboring Plasmid-Mediated Colistin Resistance: mcr-1 and mcr-3 Genes in Contracted Pig
Farms in Thailand. Front. Vet. Sci. 2020, 7, 582899. [CrossRef]
145. García-Meniño, I.; Díaz-Jiménez, D.; García, V.; de Toro, M.; Flament-Simon, S.C.; Blanco, J.; Mora, A. Genomic Characterization
of Prevalent mcr-1, mcr-4, and mcr-5 Escherichia coli Within Swine Enteric Colibacillosis in Spain. Front. Microbiol. 2019, 10, 2469.
[CrossRef]
146. Pormohammad, A.; Nasiri, M.J.; Azimi, T. Prevalence of antibiotic resistance in Escherichia coli strains simultaneously isolated
from humans, animals, food, and the environment: A systematic review and meta-analysis. Infect. Drug Resist. 2019, 12, 1181–1197.
[CrossRef]
147. Racewicz, P.; Majewski, M.; Biesiada, H.; Nowaczewski, S.; Wilczyński, J.; Wystalska, D.; Kubiak, M.; Pszczoła, M.; Madeja, Z.E.
Prevalence and characterization of antimicrobial resistance genes and class 1 and 2 integrons in multiresistant Escherichia coli
isolated from poultry production. Sci. Rep. 2022, 12, 6062. [CrossRef] [PubMed]
148. Maynard, C.; Fairbrother, J.M.; Bekal, S.; Sanschagrin, F.; Levesque, R.C.; Brousseau, R.; Masson, L.; Larivière, S.; Harel, J.
Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149:K9 isolates obtained over a 23-year period from pigs.
Antimicrob. Agents Chemother. 2003, 47, 3214–3221. [CrossRef] [PubMed]
149. Tian, X.; Zheng, X.; Sun, Y.; Fang, R.; Zhang, S.; Zhang, X.; Lin, J.; Cao, J.; Zhou, T. Molecular Mechanisms and Epidemiology
of Carbapenem-Resistant Escherichiacoli Isolated from Chinese Patients Durng 2002-2017. Infect. Drug Res. 2020, 13, 501–512.
[CrossRef] [PubMed]
150. Cormier, A.C.; Chalmers, G.; McAllister, T.A.; Cook, S.; Zaheer, R.; Scott, H.M.; Booker, C.; Read, R.; Boerlin, P. Extended-
Spectrum-Cephalosporin Resistance Genes in Escherichia coli from Beef Cattle. Antimicrob. Agents Chemother. 2016, 60, 1162–1163.
[CrossRef]
151. Gundran, R.S.; Cardenio, P.A.; Villanueva, M.A.; Sison, F.B.; Benigno, C.C.; Kreausukon, K.; Pichpol, D.; Punyapornwithaya, V.
Prevalence and distribution of blaCTX-M , blaSHV , blaTEM gene in extended- spectrum β- lactamase- producing E. coli isolates from
broiler farms in the Philippines. BMC Vet. Res. 2019, 15, 227. [CrossRef]
Antibiotics 2022, 11, 1079 35 of 40
152. Wang, M.G.; Yu, Y.; Wang, D.; Yang, R.S.; Jia, L.; Cai, D.T.; Zheng, S.L.; Fang, L.X.; Sun, J.; Liu, Y.H.; et al. The Emergence and
Molecular Characteristics of New Delhi Metallo β-Lactamase-Producing Escherichia coli From Ducks in Guangdong, China. Front.
Microbiol. 2021, 12, 677633. [CrossRef]
153. Chen, Y.; Liu, Z.; Zhang, Y.; Zhang, Z.; Lei, L.; Xia, Z. Increasing Prevalence of ESBL-Producing Multidrug Resistance
Escherichia coli from Diseased Pets in Beijing, China From 2012 to 2017. Front. Microbiol. 2019, 10, 2852. [CrossRef]
154. Ilyas, S.; Rasool, M.H.; Arshed, M.J.; Qamar, M.U.; Aslam, B.; Almatroudi, A.; Khurshid, M. The Escherichia coli Sequence Type
131 Harboring Extended-Spectrum Beta-Lactamases and Carbapenemases Genes from Poultry Birds. Infect. Drug Res. 2021, 14,
155. Ombarak, R.A.; Hinenoya, A.; Elbagory, A.M.; Yamasaki, S. Prevalence and Molecular Characterization of Antimicrobial
Resistance in Escherichia coli Isolated from Raw Milk and Raw Milk Cheese in Egypt. J. Food Protect. 2018, 81, 226–232. [CrossRef]
156. Mahmoud, N.E.; Altayb, H.N.; Gurashi, R.M. Detection of Carbapenem-Resistant Genes in Escherichia coli Isolated from Drinking
Water in Khartoum, Sudan. J. Environ. Public Health 2020, 2020, 2571293. [CrossRef]
157. Belaynehe, K.M.; Shin, S.W.; Yoo, H.S. Interrelationship between tetracycline resistance determinants, phylogenetic group
affiliation and carriage of class 1 integrons in commensal Escherichia coli isolates from cattle farms. BMC Vet. Res. 2018, 14, 340.
[CrossRef]
158. Schwaiger, K.; Hölzel, C.; Bauer, J. Resistance gene patterns of tetracycline resistant Escherichia coli of human and porcine origin.
Vet. Microbiol. 2010, 142, 329–336. [CrossRef]
159. Gholami-Ahangaran, M.; Karimi-Dehkordi, M.; Miranzadeh-Mahabadi, E.; Ahmadi-Dastgerdi, A. The frequency of tetracycline
resistance genes in Escherichia coli strains isolated from healthy and diarrheic pet birds. Iran. J. Vet. 2021, 22, 337–341.
160. Abo-Amer, A.E.; Shobrak, M.Y.; Altalhi, A.D. Isolation and antimicrobial resistance of Escherichia coli isolated from farm chickens
in Taif, Saudi Arabia. J. Glob. Antimicrob. Res. 2018, 15, 65–68. [CrossRef]
161. Belaynehe, K.M.; Won, H.G.; Yoon, I.J.; Yoo, H.S. Prevalence and molecular characteristics of 16s rRNA methylase gene rmtB in
amikacin resistant Escherichia coli isolated from South Korea. Korean J. Vet. Res. 2019, 59, 157–160. [CrossRef]
162. Usui, M.; Kajino, A.; Kon, M.; Fukuda, A.; Sato, T.; Shirakawa, T.; Kawanishi, M.; Harada, K.; Nakajima, C.; Suzuki, Y.; et al.
Prevalence of 16S rRNA methylases in Gram-negative bacteria derived from companion animals and livestock in Japan. J. Vet.
Med. Sci. 2019, 81, 874–878. [CrossRef]
163. Sigirci, B.D.; Celik, B.; Halac, B.; Adiguzel, M.C.; Kekec, I.; Metiner, K.; Ikiz, S.; Bagcigil, A.F.; Ozgur, N.Y.; Ak, S.; et al.
Antimicrobial resistance profiles of Escherichia coli isolated from companion birds. J. King Saud Univ. Sci. 2020, 32, 1069–1073.
[CrossRef]
164. Ibrahim, T.; Ngwai, Y.B.; Pennap, G.I.; Ishaleku, D.; Tsaku, P.A.; Abimiku, R.H.; Nkene, I.H.; Bassey, E.B. Antimicrobial Resistance
Profile of Salmonella Typhimurium Isolated from Commercial Poultry and Poultry Farm Handlers in Nasarawa State, Nigeria.
Microbiol. Res. J. Int. 2019, 28, 1–12. [CrossRef]
165. Derakhshandeh, A.; Eraghi, V.; Boroojeni, A.M.; Niaki, M.A.; Zare, S.; Naziri, Z. Virulence factors, antibiotic resistance genes
and genetic relatedness of commensal Escherichia coli isolates from dogs and their owners. Microb. Pathog. 2018, 116, 241–245.
[CrossRef]
166. Luque-Sastre, L.; Arroyo, C.; Fox, E.M.; McMahon, B.J.; Bai, L.; Séamus, L.F. Antimicrobial Resistance in Listeria Species. ASM J.
Microbiol. Spectr. 2018, 6, 4.
167. Iwu, C.D.; Okoh, A.I. Characterization of antibiogram fingerprints in Listeria monocytogenes recovered from irrigation water
and agricultural soil samples. PLoS ONE 2020, 15, e0228956. [CrossRef]
168. Charpentier, E.; Courvalin, P. Antibiotic resistance in Listeria spp. Antimicrob. Agents Chemother. 1999, 43, 2103–2108. [CrossRef]
[PubMed]
169. Piekarska, K. Mechanizmy oporności na fluorochinolony kodowane plazmidowo–PMQR. Post. Mikrobiol. 2018, 57, 47–57.
170. Kwiatkowska, B.; Maślińska, M. Macrolide therapy in chronic inflammatory diseases. Mediat. Inflamm. 2012, 2012, 636157.
[CrossRef] [PubMed]
171. Bertrand, S.G.; Huys, M.; Yde, K.; D’Haene, F.; Tardy, M.; Vrints, J.; Swing, J.-M.; Collard, J.M. Detection and characterization of
tet(M) in tetracycline-resistant Listeria strains from human and food-processing origins in Belgium and France. J. Med. Microbiol.
2005, 54, 1151–1156. [CrossRef] [PubMed]
172. Korsak, D.A.; Borek, S.; Daniluk, A.; Grabowska, K.; Pappelbaum, K. Antimicrobial susceptibilities of Listeria monocytogenes
strains isolated from food and food processing environment in Poland. Int. J. Food Microbiol. 2012, 158, 203–208. [CrossRef]
173. Yan, H.; Neogi, S.B.; Mo, Z.; Guan, W.; Shen, Z.; Zhang, S.; Li, L.; Yamasaki, S.; Shi, L.; Zhong, N. Prevalence and characterization
of antimicrobial resistance of foodborne Listeria monocytogenes isolates in Hebei province of Northern China, 2005-2007. Int. J.
Food Microbiol. 2010, 144, 310–316. [CrossRef] [PubMed]
174. Skarżyńska, M.; Zajac,˛ M.; Wasyl, D. Antibiotics and Bacteria: Mechanisms of Action and Resistance Strategies. Adv. Microbiol.
2020, 59, 49–62. [CrossRef]
175. Hanes, R.M.; Huang, Z. Investigation of Antimicrobial Resistance Genes in Listeria monocytogenes from 2010 through to 2021.
Int. J. Environ. Res. Public Health 2022, 19, 5506. [CrossRef]
176. Srinivasan, S.; Nam, H.M.; Nguyen, L.T.; Tamilselvam, B.; Murinda, S.E.; Oliver, S.P. Prevalence of Antimicrobial Resistance
Genes in Listeriamonocytogenes Isolated from Dairy Farms. Foodborne Pathog. Dis. 2005, 2, 201–211. [CrossRef]
Antibiotics 2022, 11, 1079 36 of 40
177. Kayode, A.; Semerjian, L.; Osaili, T.; Olapade, O.; Okoh, A. Occurrence of multidrug-resistant Listeria monocytogenes in
environmental waters: A menace of environmental and public health concern. Front. Environ. Sci. 2021, 12, 373. [CrossRef]
178. Hailu, W.; Helmy, Y.A.; Carney-Knisely, G.; Kauffman, M.; Fraga, D.; Rajashekara, G. Prevalence and Antimicrobial Resistance
Profiles of Foodborne Pathogens Isolated from Dairy Cattle and Poultry Manure Amended Farms in Northeastern Ohio, the
United States. Antibiotics 2021, 10, 1450. [CrossRef]
179. Moreno, L.Z.; Paixão, R.; Gobbi, D.D.S.; Raimundo, D.C.; Ferreira, T.P.; Moreno, A.M.; Hofer, E.; Reis, C.M.F.; Matté, G.R.; Matté,
M.H. Characterization of antibiotic resistance in Listeria spp. Isolated from slaughterhouse environments, pork and human
infections. J. Infect. Dev. Ctries. 2014, 8, 416–423. [CrossRef]
180. Skowron, K.; Wałecka-Zacharska, E.; Wiktorczyk-Kapischke, N.; Skowron, K.J.; Grudlewska-Buda, K.; Bauza-Kaszewska, J.;
Bernaciak, Z.; Borkowski, M.; Gospodarek-Komkowska, E. Assessment of the Prevalence and Drug Susceptibility of Listeria
monocytogenes Strains Isolated from Various Types of Meat. Foods 2020, 9, 1293. [CrossRef]
181. Noll, M.; Kleta, S.; Al Dahouk, S. Antibiotic susceptibility of 259 Listeria monocytogenes strains isolated from food, food-
processing plants and human samples in Germany. J. Infect. Public Health 2018, 11, 572–577. [CrossRef]
182. Jamali, H.; Paydar, M.; Ismail, S.; Looi, C.Y.; Wong, W.F.; Radmehr, B.; Abedini, A. Prevalence, antimicrobial susceptibility and
virulotyping of Listeria species and Listeria monocytogenes isolated from open-air fish markets. BMC Microbiol. 2015, 15, 144.
[CrossRef]
183. Haubert, L.; Mendonc, M.; Lopes, G.V.; de Itapema Cardoso, M.R.; da Silva, W.P. Listeria monocytogenes isolates from food and
food environment harbouring tetM and ermB resistance genes. Lett. Appl. Microbiol. 2016, 62, 23–29. [CrossRef]
184. Oswaldi, V.; Lüth, S.; Dzierzon, J.; Meemken, D.; Schwarz, S.; Feßler, A.T.; Félix, B.; Langforth, S. Distribution and Characteristics
of Listeria spp. In Pigs and Pork Production Chains in Germany. Microorganisms 2022, 10, 512. [CrossRef]
185. Davanzo, E.F.A.; dos Santos, R.L.; Castro, V.H.D.; Palma, J.M.; Pribul, B.R.; Dallago, B.S.L.; Fuga, B.; Medeiros, M.; Titze de
Almeida, S.S.; da Costa, H.M.B.; et al. Molecular characterization of Salmonella spp. And Listeria monocytogenes strains
from biofilms in cattle and poultry slaughterhouses located in the federal District and State of Goia’s, Brazil. PLoS ONE 2021,
16, e0259687.
186. Bae, D.; Smiley, R.D.; Mezal, E.H.; Khan, A.A. Characterization and Antimicrobial Resistance of Listeria monocytogenes Isolated
from Food-related Environments. Food Protect. Trends 2016, 36, 357–361.
187. Heidarzadeh, S.; Pourmand, M.R.; Hasanvand, S.; Pirjani, R.; Afshar, D.; Noori, M.; Dallal, M.M.S. Antimicrobial Susceptibility,
Serotyping, and Molecular Characterization of Antibiotic Resistance Genes in Listeria monocytogenes Isolated from Pregnant
Women with a History of Abortion. Iran. J. Public Health 2020, 50, 170–179. [CrossRef] [PubMed]
188. EFSA. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals
and food in 2017. EFSA J. 2019, 17, 5598.
189. EFSA; ECDC. The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food-borne
Outbreaks in 2014. EFSA J. 2015, 13, 4329.
190. Crump, J.A.; Sjölund-Karlsson, M.; Gordon, M.A.; Parry, C.M. Epidemiology, Clinical Presentation, Laboratory Diagnosis,
Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections. Clin. Microbiol. Rev. 2015, 4, 901–937.
[CrossRef] [PubMed]
191. Grünberg, W. Salmonellosis in Animals. 2020. Available online: https://www.msdvetmanual.com/digestive-system/
salmonellosis/salmonellosis-in-animals (accessed on 21 July 2021).
192. Rozporzadzenie
˛ Ministra Rolnictwa i Rozwoju Wsi z dnia 10 Lutego 2022 r. w Sprawie Wprowadzenia “Krajowego Programu
Zwalczania Niektórych Serotypów Salmonella w Stadach kur Niosek Gatunku Gallus Gallus” na 2022 r. (Dz. U. z 2020 r.
poz. 1421). Available online: https://www.infor.pl/akt-prawny/DZU.2022.048.0000413,rozporzadzenie-ministra-rolnictwa-i-
rozwoju-wsi-w-sprawie-wprowadzenia-krajowego-programu-zwalczania-niektorych-serotypow-salmonella-w-stadach-kur-
niosek-gatunku-gallus-gallus-na-2022-r.html (accessed on 10 February 2022).
193. Li, Y.A.; Chen, Y.; Du, Y.Z.; Guo, W.; Chu, D.; Fan, J.; Wang, X.; Bellefleur, M.; Wang, S.; Shi, H. Live-attenuated Salmonella enterica
serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice. BMC
Vet. Res. 2020, 16, 129. [CrossRef] [PubMed]
194. Nishino, K.; Nikaido, E.; Yamaguchi, A. Regulation and physiological function of multidrug efflux pumps in Escherichia coli and
Salmonella. Biochim. Biophys. Acta 2009, 794, 834–843. [CrossRef] [PubMed]
195. Cloeckaert, A. AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium DT104.
Antimicrob. Agents Chemother. 2004, 48, 3729–3735.
196. Burmølle, M.; Webb, J.S.; Rao, D.; Hansen, L.H.; Sørensen, S.J.; Kjelleberg, S. Enhanced Biofilm Formation and Increased Resistance
to Antimicrobial Agents and Bacterial Invasion Are Caused by Synergistic Interactions in Multispecies Biofilms. Appl. Environ.
Microbiol. 2006, 72, 3916–3923. [CrossRef]
197. Michael, G.B.; Schwarz, S. Antimicrobial resistance in zoonotic nontyphoidal Salmonella: An alarming trend? Clin. Microbiol.
Infect. 2016, 22, 968–974. [CrossRef]
198. Yoneyama, H.; Katsumata, R. Antibiotic resistance in bacteria and its future for novel antibiotic development. Biosci. Biotechnol.
Biochem. 2006, 70, 1060–1075. [CrossRef]
199. Gonzalez, L.S.; Spencer, J.P. Aminoglycosides: A practical review. Am. Fam. Physician 1998, 58, 1811–1820.
Antibiotics 2022, 11, 1079 37 of 40
200. Shaw, K.J.; Rather, P.N.; Hare, R.S.; Miller, G.H. Molecular genetics of aminoglycoside resistance genes and familial relationships
of the aminoglycoside-modifying enzymes. Microbiol. Rev. 1993, 57, 138–163. [CrossRef]
201. Gebreyes, W.A.; Altier, C. Molecular characterization of multidrug-resistant Salmonella enterica subsp. Enterica serovar Ty-
phimurium isolates from swine. J. Clin. Microbiol. 2002, 40, 2813–2822. [CrossRef]
202. Savic, M.; Lovric, J.; Tomic, T.I.; Vasiljevic, B.; Conn, G.L. Determination of the target nucleosides for members of two families of
16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids
Res. 2009, 37, 5420–5431. [CrossRef]
203. Sun, S.; Selmer, M.; Andersson, D.I. Resistance to β-lactam antibiotics conferred by point mutations in penicillin-binding proteins
PBP3, PBP4 and PBP6 in Salmonella enterica. PLoS ONE 2014, 9, e97202. [CrossRef]
204. Uddin, M.J.; Ahn, J. Characterization of β-lactamase- and efflux pump-mediated multiple antibiotic resistance in Salmonella
Typhimurium. Food Sci. Biotechnol. 2018, 27, 921–928. [CrossRef]
205. Souza, A.I.S.; Saraiva, M.M.S.; Casas, M.R.T.; Monique, R.T.; Casas, G.M.; Oliveira, M.V.; Cardozo, V.P.; Benevides, F.O.; Barbosa,
O.C.; Freitas Neto, A.M.; et al. High occurrence of β-lactamase-producing Salmonella Heidelberg from poultry origin. PLoS ONE
2020, 15, e0230676.
206. Leverstein-van Hall, M.A.; Dierikx, C.M.; Stuart, J.C.; Voets, G.M.; van den Munckhof, M.P.; van Essen-Zandbergen, A.; Platteel,
T.; Fluit, A.C.; van de Sande-Bruinsma, N.; Scharinga, J.; et al. Dutch patients, retail chicken meat and poultry share the same
ESBL genes, plasmids and strains. Clin. Microbiol. Infect. 2011, 17, 873–880. [CrossRef]
207. Smith, A.L.; Weber, A. Pharmacology of chloramphenicol. Pediatr. Clin. N. Am. 1983, 30, 209–236. [CrossRef]
208. Guerra, B.; Soto, S.; Cal, S.; Mendoza, M.C. Antimicrobial resistance and spread of class 1 integrons among Salmonella serotypes.
Antimicrob. Agents Chemother. 2000, 44, 2166–2169. [CrossRef]
209. Chen, S.; Zhao, S.H.; White, D.G.; Schroeder, C.M.; Lu, R.; Yang, H.C.; McDermott, P.F.; Ayers, S.; Meng, J. Characterization of
multiple-antimicrobial-resistant Salmonella serovars isolated from retail meats. Appl. Environ. Microbiol. 2004, 70, 1–7. [CrossRef]
210. White, D.G.; Zhao, S.; Sudler, R.; Ayers, S.; Friedman, S.; Chen, S.; Meng, J. The isolation of antibiotic-resistant Salmonella from
retail ground meats. N. Engl. J. Med. 2001, 345, 1147–1154. [CrossRef]
211. Alcaine, S.D.; Sukhnanand, S.S.; Warnick, L.D.; Su, W.L.; McGann, P.; McDonough, P.; Wiedmann, M. Ceftiofur-resistant Salmonella
strains isolated from dairy farms represent multiple widely distributed subtypes that evolved by independent horizontal gene
transfer. Antimicrob. Agents Chemother. 2005, 49, 4061–4067. [CrossRef]
212. Cabrera, R.; Ruiz, J.; Marco, F.; Oliveira, I.; Arroyo, M.; Aladuena, A.; Usera, M.A.; Jimenez De Anta, M.T.; Gascon, J.; Vila, J.
Mechanism of resistance to several antimicrobial agents in Salmonella Clinical isolates causing traveler’s diarrhea. Antimicrob.
213. Mascaretti, O.A. Bacteria versus Antimicrobial Agents: An Integrated Approach; ASM Press: Washington, DC, USA, 2003.
214. Chopra, I.; Roberts, M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial
resistance. Microbiol. Mol. Biol. Rev. 2001, 65, 232–260. [CrossRef] [PubMed]
215. Pezzella, C.; Ricci, A.; DiGiannatale, E.; Luzzi, I.; Carattoli, A. Tetracycline and streptomycin resistance genes, transposons,
and plasmids in Salmonella enterica isolates from animals in Italy. Antimicrob. Agents Chemother. 2004, 48, 903–908. [CrossRef]
[PubMed]
216. Carattoli, A.; Villa, L.; Feudi, C.; Curcio, L.; Orsini, S.; Luppi, A.; Pezzotti, G.; Magistrali, C.F. Novel plasmid-mediated colistin
resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Eurosurveillance 2017,
22, 30589. [CrossRef] [PubMed]
217. El Garch, F.; Sauget, M.; Hocquet, D.; LeChaudee, D.; Woehrle, F.; Bertrand, X. mcr-1 is borne by highly diverse Escherichia coli
isolates since 2004 in food-producing animals in Europe. Clin. Microbiol. Infect. 2017, 23, 51.e1–51.e4. [CrossRef] [PubMed]
218. Antunes, P.J.; Machado, J.C.; Sousa, P.L. Dissemination ofsulfonamide resistance genes (sul1, sul2, and sul3) in Portuguese
Salmonella enterica strains and relation with integrons. Antimicrob. Agents Chemother. 2005, 49, 836–839. [CrossRef]
219. Chen, S.; Cui, S.; McDermott, P.F.; Zhao, S.; White, D.G.; Paulsen, I.; Meng, J. Contribution of target gene mutations and efflux to
decreased susceptibility of Salmonella enterica serovar Typhimurium to fluoroquinolones and other antimicrobials. Antimicrob.
220. Gast, R.K.; Guraya, R.; Jones, D.R.; Anderson, K.E. Persistence of fecal shedding of Salmonella Enteritidis by experimentally
infected laying hens housed in conventional or enriched cages. Poult. Sci. 2015, 94, 1650–1656. [CrossRef]
221. Xie, T.; Wu, G.; He, X.; Lai, Z.; Zhang, H.; Zhao, J. Antimicrobial resistance and genetic diversity of Salmonella enterica from eggs.
Food Sci. Nutr. 2019, 7, 2847–2853. [CrossRef]
222. Tadesse, G.; Mitiku, H.; Teklemariam, Z.; Marami, D. Salmonella and Shigella among Asymptomatic Street Food Vendors in
the Dire Dawa city, Eastern Ethiopia: Prevalence, Antimicrobial Susceptibility Pattern, and Associated Factors. Environ. Health
Insights 2019, 13, 1–8. [CrossRef]
223. Shukla, P.; Bansode, F.W.; Singh, R.K. Chloramphenicol Toxicity: A Review. J. Med. Med. Sci. 2011, 2, 1313–1316.
224. Ibrahim, R.A.; Cryer, T.L.; Lafi, S.Q.; Basha, E.A.; Good, L.; Tarazi, Y.H. Identification of Escherichia coli from broiler chickens in
Jordan, their antimicrobial resistance, gene characterization and the associated risk factors. BMC Vet. Res. 2019, 15, 159. [CrossRef]
225. Castro-Vargas, R.; Fandiño-de-Rubio, L.C.; Vega, A.; Rondón-Barragán, I. Phenotypic and Genotypic Resistance of Salmonella
Heidelberg Isolated from One of the Largest Poultry Production Region from Colombia. Int. J. Poult. Sci. 2019, 18, 610–617.
[CrossRef]
Antibiotics 2022, 11, 1079 38 of 40
226. Rodney, S.; Umakanth, S.; Chowdhury, G.; Saha, R.N.; Mukhopadhyay, A.K.; Ballal, M. Poultry: A receptacle for non-typhoidal
Salmonellae and antimicrobial resistance. Iran. J. Microbiol. 2019, 11, 31–38.
227. Yang, J.; Gao, S.; Chang, Y.; Su, M.; Xie, Y.; Sun, S. Occurrence and Characterization of Salmonella Isolated from Large-Scale
Breeder Farms in Shandong Province, China. Biomed. Res. Int. 2019, 2019, 8159567. [CrossRef]
228. Roth, N.; Käsbohrer, A.; Mayrhofer, S.; Zitz, U.; Hofacre, C.; Domig, K.J. The application of antibiotics in broiler production and
the resulting antibiotic resistance in Escherichia coli: A global overview. Poult. Sci. 2019, 98, 1791–1804. [CrossRef]
229. John, J., Jr. The treatment of resistant staphylococcal infections. F1000 Res. 2020, 9, 150. [CrossRef]
230. Shariati, A.; Dadashi, M.; Moghadam, M.T.; van Belkum, A.; Yaslianifard, S.; Darban-Sarokhalil, D. Global prevalence and
distribution of vancomycin resistant, vancomycin intermediate and heterogeneously vancomycin intermediate Staphylococcus
aureus clinical isolates: A systematic review and meta-analysis. Sci. Rep. 2020, 10, 12689. [CrossRef] [PubMed]
231. Szymanek-Majchrzak, K.; Mlynarczyk, A.; Mlynarczyk, G. Characteristics of glycopeptide-resistant Staphylococcus aureus strains
isolated from inpatients of three teaching hospitals in Warsaw, Poland. Antimicrob. Resist. Infect. Control 2021, 7, 105. [CrossRef]
[PubMed]
232. Roy, J.P.; Keefe, G. Systematic review: What is the best antibiotic treatment for Staphylococcus aureus intramammary infection of
lactating cows in North America? Vet. Clin. N. Am. Food Anim. Pract. 2012, 28, 39–50. [CrossRef] [PubMed]
233. Apley, M.D.; Coetzee, J.F. Antimicrobial Therapy in Veterinary Medicine, 5th ed.; Wiley-Blackwell: Hoboken, NJ, USA, 2013;
pp. 495–518.
234. Mala, L.; Lalouckova, K.; Skrivanova, E. Bacterial Skin Infections in Livestock and Plant-Based Alternatives to Their Antibiotic
Treatment. Animals 2021, 11, 2473. [CrossRef]
235. Rafailidis, P.I.; Kofteridis, D. Proposed amendments regarding the definitions of multidrug-resistant and extensively drug-resistant
bacteria. Expert Rev. Anti-Infect. Ther. 2022, 20, 139–146. [CrossRef]
236. Emaneini, M.; Bigverdi, R.; Kalantar, D.; Soroush, S.; Jabalameli, F.; Khoshgnab, B.N.; Asadollahi, P.; Taherikalani, M. Distribution
of genes encoding tetracycline resistance and aminoglycoside modifying enzymes in Staphylococcus aureus strains isolated from
a burn center. Ann. Burn. Fire Disasters 2013, 26, 76–80.
237. Lyon, B.R.; Skurray, R.A. Antimicrobial resistance of Staphylococcus aureus: Genetic basis. Microbiol. Rev. 1987, 51, 88–134.
[CrossRef]
238. Gómez, P.; Lozano, C.; Camacho, M.C.; Lima-Barberov, J.F.; Hernández, J.M.; Zarazaga, M.; Höfle, U.; Torres, C. Detection of
MRSA ST3061-t843-mecC and ST398-t011-mecA in white stork nestlings exposed to human residues. J. Antimicrob. Chemother.
2016, 71, 53–57. [CrossRef]
239. Podkowik, M.; Bystroń, J.; Bania, J. Prevalence of antibiotic resistance genes in staphylococci isolated from ready-to-eat meat
products. Pol. J. Vet. Sci. 2012, 15, 233–237. [CrossRef]
240. Schwarz, S.; Loeffler, A.; Kadlec, K. Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine.
Vet. Dermatol. 2017, 28, 82-e19.
241. Wendlandt, S.; Shen, J.; Kadlec, K.; Wang, Y.; Li, B.; Zhang, W.J.; Feßler, A.T.; Wu, C.; Schwarz, S. Multidrug resistance genes in
staphylococci from animals that confer resistance to critically and highly important antimicrobial agents in human medicine.
Trends Microbiol. 2015, 23, 44–54. [CrossRef]
242. Lüthje, P.; Schwarz, S. Molecular basis of resistance to macrolides and lincosamides among staphylococci and streptococci from
various animal sources collected in the resistance monitoring program BfT-GermVet. Int. J. Antimicrob. Agents 2007, 29, 528–535.
[CrossRef]
243. Sudagidan, M.; Aydin, A. Virulence properties of Staphylococcus delphini strains isolated from domestic pigeons. Med. Weter.
2012, 68, 231–236.
244. Kizerwetter-Świda, M.; Chrobak-Chmiel, D.; Rzewuska, M.; Binek, M. Resistance of canine methicillin-resistant Staphylococcus
pseudintermedius strains to pradooxacin. J. Vet. Diagn. Investig. 2016, 28, 514–518. [CrossRef]
245. Perumal, N.S.; Murugesan, P.; Krishnan, P. Distribution of genes encoding aminoglycoside-modifying enzymes among clinical
isolates of methicillin-resistant staphylococci. Indian J. Med. Microbiol. 2016, 34, 350. [CrossRef]
246. Klingenberg, C.; Sundsfjord, A.; Rønnestad, A.; Mikalsen, J.; Gaustad, P.; Flægstad, T. Phenotypic and genotypic aminoglycoside
resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989–2000. J.
Antimicrob. Chemother. 2004, 54, 889–896. [CrossRef]
247. Yoshida, H.; Bogaki, M.; Nakamura, M.; Nakamura, S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of
Escherichia coli. Antimicrob. Agents Chemother. 1990, 34, 1271–1272. [CrossRef]
248. Jacoby, G.A.; Strahilevitz, J.; Hooper, D.C. Plasmid-mediated quinolone resistance. Microbiol. Spectr. 2014, 2, 1–24. [CrossRef]
249. Truong-Bolduc, Q.C.; Strahilevitz, J.; Hooper, D.C. NorC, a new efflux pump regulated by MgrA of Staphylococcus aureus.
Antimicrob. Agents Chemother. 2006, 50, 1104–1107. [CrossRef]
250. Wendlandt, S.; Feßler, A.T.; Monecke, S.; Ehricht, R.; Schwarz, S.; Kadlec, K. The diversity of antimicrobial resistance genes among
staphylococci of animal origin. Int. J. Med. Microbiol. 2013, 303, 338–349. [CrossRef]
251. Schwarz, S.; Werckenthin, C.; Kehrenberg, C. Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in
Staphylococcus sciuri. Antimicrob. Agents Chemother. 2000, 44, 2530–2533. [CrossRef] [PubMed]
252. Li, J.; Jiang, N.; Ke, Y.; Feßler, A.T.; Wang, Y.; Schwarz, S.; Wu, C. Characterization of pig-associated methicillin-resistant
Staphylococcus aureus. Vet. Microbiol. 2017, 201, 183–187. [CrossRef] [PubMed]
Antibiotics 2022, 11, 1079 39 of 40
253. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/Country%20summaries-AER-EARS-Net%20

202019.pdf (accessed on 1 June 2022).
254. Pexara, A.; Solomakos, N.; Govaris, A. Occurrence, antibiotic resistance and enteroxigenicity of Staphylococcus spp. in tonsils of
slaughtered pigs in Greece. Lett. Appl. Microbiol. 2020, 71, 394–399. [CrossRef] [PubMed]
255. Mourabit, N.; Arakrak, A.; Bakkali, M.; Zian, Z.; Bakkach, J.; Laglaoui, A. Antimicrobial Resistance Trends In Staphylococcus
Aureus Strains Carried by Poultry In North of Morocco: A Preliminary Analysis. J. Food Qual. 2021, 2021, 8856004. [CrossRef]
256. Syed, M.A.; Ullah, H.; Tabassum, S.; Fatima, B.; Woodley, T.A.; Ramadan, H.; Jackson, C.R. Staphylococci in poultry intestines: A
comparison between farmed and household chickens. Poult. Sci. 2020, 99, 4549–4557. [CrossRef]
257. Aarestrup, F.; Engberg, J. Antimicrobial resistance of thermophilic Campylobacter. Vet. Res. 2001, 32, 311–321. [CrossRef]
258. Engberg, J.; Aarestrup, F.M.; Taylor, D.E.; Gerner-Smidt, P.; Nachamkin, I. Quinolone and macrolide resistance in Campylobacter
jejuni and C. coli: Resistance mechanisms and trends in human isolates. Emerg. Infect. Dis. 2001, 7, 24–34. [CrossRef]
259. Piddok, L.J.V. Quinolone resistance and Campylobacter spp. J. Antimicrob. Chemother. 1995, 36, 891–898. [CrossRef]
260. Taylor, D.E.; Garner, R.S.; Allan, B.J. Characterization of tetracycline resistance plasmids from Campylobacter jejuni and
Campylobacter coli. Antimicrob. Agents Chemother. 1983, 24, 930–935. [CrossRef]
261. Burridge, R.; Warren, C.; Phillips, I. Macrolide, lincosamide and streptogramin resistance in Campylobacter jejuni/coli. J. Antimicrob.
262. Rautelin, H.; Renkonen, O.V.; Kosunen, T.U. Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter
coli in subjects from Finland. Antimicrob. Agents Chemother. 1991, 35, 2065–2069. [CrossRef]
263. Endtz, H.P.; Ruijs, G.J.; van Klingeren, B.; Jansen, W.H.; van der Reyden, T.; Mouton, R.P. Quinolone resistance in Campylobacter
isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J. Antimicrob. Chemother.
1991, 27, 199–208. [CrossRef]
264. Nachamkin, I.; Ung, H.; Li, M. Increasing fluoroquinolone resistance in Campylobacter jejuni, Pennsylvania, USA, 1982–2001.
Emerg. Infect. Dis. 2002, 8, 1501–1503. [CrossRef]
265. Gurung, S.; Kafle, S.; Dhungel, B.; Adhikari, N.; Shrestha, U.T.; Adhikari, B.; Banjara, M.R.; Rijal, K.R.; Ghimire, P. Detection of
oxa-48 gene in carbapenem-resistant escherichia coli and klebsiella pneumoniae from urine samples. Infect. Drug Resist. 2020, 13,
2311–2321. [CrossRef]
266. Pärnänen, K.M.M.; Narciso-Da-Rocha, C.; Kneis, D.; Berendonk, T.U.; Cacace, D.; Do, T.T.; Elpers, C.; Fatta-Kassinos, D.;
Henriques, I.; Jaeger, T.; et al. Antibiotic resistance in European wastewater treatment plants mirrors the pattern of clinical
antibiotic resistance prevalence. Sci. Adv. 2019, 5, eaau9124. [CrossRef]
267. D’Andrea, M.M.; Venturelli, C.; Giani, T.; Arena, F.; Conte, V.; Bresciani, P.; Rumpianesi, F.; Pantosti, A.; Narni, F.; Rossolini, G.M.
Persistent carriage and infection by multidrug-resistant Escherichia coli ST405 producing NDM-1 carbapenemase: Report on the
first Italian cases. J. Clin. Microbiol. 2011, 49, 2755–2758. [CrossRef]
268. Sidjabat, H.E.; Townsend, K.M.; Hanson, N.D.; Bell, J.M.; Stokes, H.W.; Gobius, K.S.; Moss, S.M.; Trott, D.J. Identification of
blaCMY-7 and associated plasmid-mediated resistance genes in multidrug-resistant Escherichia coli isolated from dogs at a
veterinary teaching hospital in Australia. J. Antimicrob. Chemother. 2006, 57, 840–848. [CrossRef]
269. Hassan, I.Z.; Wandrag, B.; Gouws, J.J.; Qekwana, D.N.; Naidoo, V. Antimicrobial resistance and mcr-1 gene in Escherichia coli
isolated from poultry samples submitted to a bacteriology laboratory in South Africa. Vet. World 2021, 14, 2662–2669. [CrossRef]
270. Li, X.S.; Wang, G.Q.; Du, X.D.; Cui, B.A.; Zhang, S.M.; Shen, J.Z. Antimicrobial susceptibility and molecular detection of
chloramphenicol and florfenicol resistance among Escherichia coli isolates from diseased chickens. J. Vet. Sci. 2007, 8, 243–247.
[CrossRef]
271. Fioriti, S.; Morroni, G.; Coccitto, S.N.; Brenciani, A.; Antonelli, A.; Di Pilato, V.; Baccani, I.; Pollini, S.; Cucco, L.; Morelli, A.; et al.
Detection of oxazolidinone resistance genes and characterization of genetic environments in enterococci of Swine origin, Italy.
Microorganisms 2020, 8, 2021. [CrossRef]
272. Yang, F.; Zhang, S.; Shang, X.; Wang, X.; Yan, Z.; Li, H.; Li, J. Short communication: Antimicrobial resistance and virulence genes
of Enterococcus faecalis isolated from subclinical bovine mastitis cases in China. J. Dairy Sci. 2019, 102, 140–144. [CrossRef]
[PubMed]
273. Farman, M.; Yasir, M.; Al-Hindi, R.R.; Farraj, S.A.; Jiman-Fatani, A.A.; Alawi, M.; Azhar, E.I. Genomic analysis of multidrug-
resistant clinical Enterococcus faecalis isolates for antimicrobial resistance genes and virulence factors from the western region of
Saudi Arabia. Antimicrob. Resist. Infect. Control 2019, 8, 1–11. [CrossRef] [PubMed]
274. Mirnejad, R.; Sajjadi, N.; Zavaryani, S.M.; Piranfar, V.; Hajihosseini, M.; Roshanfekr, M. Identification of aminoglycoside resistance
genes by Triplex PCR in Enterococcus spp. isolated from ICUs. Infez. Med. 2016, 24, 222–229. [PubMed]
275. Sekyere, J.O.; Mensah, E. Molecular epidemiology and mechanisms of antibiotic resistance in Enterococcus spp., Staphylococcus
spp., and Streptococcus spp. in Africa: A systematic review from a One Health perspective. Ann. N. Y. Acad. Sci. 2020, 1465,
29–58. [CrossRef] [PubMed]
276. Výrostková, J.; Regecová, I.; Dudriková, E.; Marcinčák, S.; Vargová, M.; Kováčová, M.; Mal’ová, J. Antimicrobial Resistance of
Enterococcus sp. Isolated from Sheep and Goat Cheeses. Foods 2021, 10, 1844. [CrossRef] [PubMed]
277. Holman, D.B.; Klima, C.L.; Gzyl, K.E.; Zaheer, R.; Service, C.; Jones, T.H.; McAllister, T.A. Antimicrobial Resistance in Enterococcus
spp. Isolated from a Beef Processing Plant and Retail Ground Beef. Microbiol. Spectr. 2021, 9, e01980-21. [CrossRef] [PubMed]
Antibiotics 2022, 11, 1079 40 of 40
278. El-Zamkan, M.A.; Mohamed, H.M.A. Antimicrobial resistance, virulence genes and biofilm formation in Enterococcus species
isolated from milk of sheep and goat with subclinical mastitis. PLoS ONE 2021, 16, 1–19. [CrossRef]
279. Zaheer, R.; Cook, S.R.; Barbieri, R.; Goji, N.; Cameron, A.; Petkau, A.; Polo, R.O.; Tymensen, L.; Stamm, C.; Song, J.; et al.
Surveillance of Enterococcus spp. reveals distinct species and antimicrobial resistance diversity across a One-Health continuum.
Sci. Rep. 2020, 10, 1–16. [CrossRef]
280. Filiousis, G.; Johansson, A.; Frey, J.; Perreten, V. Prevalence, genetic diversity and antimicrobial susceptibility of Listeria
monocytogenes isolated from open-air food markets in Greece. Food Control 2009, 20, 314–317. [CrossRef]
281. Mpondo, L.; Ebomah, K.E.; Okoh, A.I. Multidrug-resistant listeria species shows abundance in environmental waters of a key
district municipality in South Africa. Int. J. Environ. Res. Public Health 2021, 18, 481. [CrossRef]
282. Chen, B.Y.; Pyla, R.; Kim, T.J.; Silva, J.L.; Jung, Y.S. Antibiotic resistance in Listeria species isolated from catfish fillets and
processing environment. Lett. Appl. Microbiol. 2010, 50, 626–632. [CrossRef]
283. Escolar, C.; Gómez, D.; García, M.D.C.R.; Conchello, P.; Herrera, A. Antimicrobial Resistance Profiles of Listeria monocytogenes
and Listeria innocua Isolated from Ready-to-Eat Products of Animal Origin in Spain. Foodborne Pathog. Dis. 2017, 14, 357–363.
[CrossRef]
284. Roberts, M.C.; Facinelli, B.; Giovanetti, E.; Varaldo, P.E. Transferable erythromycin resistance in Listeria spp. isolated from food.
Appl. Environ. Microbiol. 1996, 62, 269–270. [CrossRef]
285. Onohuean, H.; Igere, B.E. Occurrence, Antibiotic Susceptibility and Genes Encoding Antibacterial Resistance of Salmonella
spp. and Escherichia coli From Milk and Meat Sold in Markets of Bushenyi District, Uganda. Microbiol. Insights 2022, 15,
11786361221088992. [CrossRef]
286. Zishiri, O.T.; Mkhize, N.; Mukaratirwa, S. Prevalence of virulence and antimicrobial resistance genes in Salmonella spp. isolated
from commercial chickens and human clinical isolates from south Africa and Brazil. Onderstepoort J. Vet. Res. 2016, 83, 1–11.
[CrossRef]
287. Ferreira, A.; Pavelquesi, S.; Monteiro, E.; Rodrigues, L.; Silva, C.; Silva, I.; Orsi, D. Prevalence and Antimicrobial Resistance of
Salmonella spp. in Aquacultured Nile Tilapia (Oreochromis niloticus) Commercialized in Federal District, Brazil. Foodborne
Pathog. Dis. 2021, 18, 778–783. [CrossRef]
288. Pławińska-Czarnak, J.; Wódz, K.; Kizerwetter-Świda, M.; Bogdan, J.; Kwieciński, P.; Nowak, T.; Strzałkowska, Z.; Anusz, K.
Multi-Drug Resistance to Salmonella spp. When Isolated from Raw Meat Products. Antibiotics 2022, 11, 876. [CrossRef]
289. Lynne, A.M.; Rhodes-Clark, B.S.; Bliven, K.; Zhao, S.; Foley, S.L. Antimicrobial resistance genes associated with Salmonella
enterica serovar newport isolates from food animals. Antimicrob. Agents Chemother. 2008, 52, 353–356. [CrossRef]
290. Lauteri, C.; Festino, A.R.; Conter, M.; Vergara, A. Prevalence and antimicrobial resistance profile in Salmonella spp. isolates from
swine food chain. Ital. J. Food Saf. 2022, 11, 9980. [CrossRef]
291. Arkali, A.; Çetinkaya, B. Molecular identification and antibiotic resistance profiling of Salmonella species isolated from chickens
in eastern Turkey. BMC Vet. Res. 2020, 16, 1–8. [CrossRef]
292. Ranjbar, R.; Dehkordi, F.S.; Heiat, M. The frequency of resistance genes in salmonella enteritidis strains isolated from cattle. Iran.
J. Public Health 2020, 49, 968–974. [CrossRef]
293. Sisak, F.; Havlickova, H.; Hradecka, H.; Rychlik, I.; Kolackova, I.; Karpiskova, R. Antibiotic resistance of Salmonella spp. isolates
from pigs in the Czech Republic. Vet. Med. 2006, 51, 303–310. [CrossRef]
294. Marek, A.; Pyzik, E.; St˛epień-Pyśniak, D.; Urban-Chmiel, R.; Jarosz, Ł.S. Association Between the Methicillin Resistance of
Staphylococcus aureus Isolated from Slaughter Poultry, Their Toxin Gene Profiles and Prophage Patterns. Curr. Microbiol. 2018,
75, 1256–1266. [CrossRef]
295. Osada, M.; Aung, M.S.; Urushibara, N.; Kawaguchiya, M.; Ohashi, N.; Hirose, M.; Kobayashi, N. Prevalence and Antimicrobial
Resistance of Staphylococcus aureus and Coagulase-Negative Staphylococcus/Mammaliicoccus from Retail Ground Meat:
Identification of Broad Genetic Diversity in Fosfomycin Resistance Gene fosB. Pathogens 2022, 11, 469. [CrossRef]
296. Duran, N.; Ozer, B.; Duran, G.G.; Onlen, Y.; Demir, C. Antibiotic resistance genes & susceptibility patterns in staphylococci. Indian
J. Med. Res. 2012, 135, 389–396.
297. Yigrem, C.; Eribo, B.; Sangre, K. Incidence of Antibiotic Resistant Staphylococcus aureus in Leafy Greens and Clinical Sources. J.
Microbiol. Res. 2022, 12, 13–23. [CrossRef]
298. Manoharan, M.; Sistla, S.; Ray, P. Prevalence and Molecular Determinants of Antimicrobial Resistance in Clinical Isolates of
Staphylococcus haemolyticus from India. Microb. Drug Resist. 2021, 27, 501–508. [CrossRef]
299. Mesbah, A.; Mashak, Z.; Abdolmaleki, Z. A survey of prevalence and phenotypic and genotypic assessment of antibiotic resistance
in Staphylococcus aureus bacteria isolated from ready-to-eat food samples collected from Tehran Province, Iran. Trop. Med. Health
2021, 49, 1–12. [CrossRef]
300. Schlegelova, J.; Vlkova, H.; Babak, V.; Holasova, M.; Jaglic, Z.; Stosova, T.; Sauer, P. Resistance to erythromycin of
Staphylococcus spp. isolates from the food chain. Vet. Med. 2008, 53, 307–314. [CrossRef]
301. Osman, K.; Badr, J.; Al-Maary, K.S.; Moussa, I.M.I.; Hessain, A.M.; Girah, Z.M.S.A.; Abo-shama, U.H.; Orabi, A.; Saad, A.
Prevalence of the antibiotic resistance genes in coagulase-positive-and negative-staphylococcus in chicken meat retailed to
consumers. Front. Microbiol. 2016, 7, 1846. [CrossRef] [PubMed]
302. França, C.A.; Peixoto, R.M.; Cavalcante, M.B.; Melo, N.F.; Oliveira, C.J.B.; Veschi, J.L.A.; Mota, R.A.; Costa, M.M. Antimicrobial
resistance of Staphylococcus spp. from small ruminant mastitis in Brazil. Pesq. Vet. Bras. 2012, 32, 747–753. [CrossRef]

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antibiotics

Antibiotics 2022, 11, 1079. https://doi.org/10.3390/antibiotics11081079 https://www.mdpi.com/journal/antibiotics

2. Mechanisms of Acquisition of Drug Resistance among Bacteria

anism of action of an antibacterial compound, and acquisition of foreign DNA encoding

3. Mechanisms of Transfer of Resistance Based on Examples of Various Species

3.1.1. Resistance to Fluoroquinolones

3.1.2. Resistance to Macrolides

3.1.3. Resistance to Tetracyclines

3.1.4. Resistance to β-Lactams

Table 1. Examples of prevalence of antimicrobial-resistant Campylobacter spp. isolated from various

Resistance to Antimicrobials (Resistance

13.8 (Burkina Faso); 20.1 (Australia); 50.0 (Ethiopia);

0 (Lithuania); 0.6 (Poland); 1.8 (Australia); 2.0–28.6

10.3 (Burkina Faso); 15.6 (Australia); 49.7–85.7 (Belgium);

3.2. Enterococcus spp.

3.2.1. Resistance to β-Lactam Antibiotics

3.2.2. Resistance to Inhibitors of the Third Step of Peptidoglycan Synthesis—Glycopeptides

3.2.3. Resistance to Aminoglycosides

The HLSR (high-level streptomycin resistance) phenotype means a high level of

3.2.4. Resistance to Tetracyclines

3.2.5. Resistance to Macrolides, Lincosamides and Streptogramins

3.2.6. Resistance to Antimetabolites—Sulphonamides and Trimethoprim

sulfamethoxazole inhibits two consecutive steps in the tetrahydrofolate synthesis pathway,

3.2.7. Resistance to Fluoroquinolones

3.3. Escherichia coli

E. coli infections in animals are subjected to various pharmaceutical treatments. For

3.3.1. Resistance to β-Lactams

3.3.2. Resistance to Fluoroquinolones

3.3.3. Resistance to Aminoglycosides

3.3.4. Resistance to Tetracyclines

3.3.5. Resistance to Sulphonamides and Trimethoprim

3.3.6. Resistance to Phenicols

3.3.7. Resistance to Polymyxins

blaVIM 28 - - 23.7 - - - Nowaczek et al. [135]

blaNDM 4–51.7 - - 31.8–19.8 2.36 - -

tet(C) 7.2 5.4 25–5.1 1.7 - 4.3 - Belaynehe et al. [157];

qepA 3.6 - 4.5 1.3 - - 2.6

strA/B 61.2/63.8 76.7 52.6/54.7 - 2/3 18.4 28

sulIII 3.3 - 7.6–2.2 - - 0.9–1.35 -

mcr-1 - 11.5 4.45–20.6 25.0 2.36 14.9 -

Belaynehe et al. [157];

3.4. Listeria spp.

3.4.1. Resistance to Fluoroquinolones

3.4.2. Resistance to Macrolides

3.4.3. Resistance to Tetracyclines

3.5. Resistance to β-Lactams

In the case of L. monocytogenes strains obtained from groundwater in agricultural

Table 3. Prevalence of specific genes of resistance to selected antibiotics in Listeria spp.

tet(A) 32 0 85.2 23 - 35.7 0 Srinivasan et al. [176];

tet(B) 19 38 3.3 Iwu & Okoh, [167];

vgaD 100 13 100

vanA - 0 0 4.65 0 - - Jamali et al. [182];

floR 66 4 0 - - - 0 Srinivasan et al. [176];

3.6. Salmonella spp.

3.6.1. Resistance to Aminoglycosides

3.6.2. Resistance to β-Lactams

drugs differ between genera of bacteria, resulting in differences in the effectiveness of

3.6.3. Resistance to Phenicols

3.6.4. Resistance to Tetracyclines

3.6.5. Resistance to Colistin