Bacterial Mechanisms of

Pathogenicity

4th Lecture
4. Toxins
◗ Poisonous substances produced by
microorganisms
◗ toxins - primary factor - pathogenicity
◗ 220 known bacterial toxins
• 40% cause disease by damaging the Eukaryotic
cell membrane
◗ Toxemia
• Toxins in the bloodstream
• Toxigenicity: Capacity of microorganisms to
produce toxins.
Two Types of Toxins
◗ 1. Exotoxins
• secreted outside the bacterial cell

◗ 2. Endotoxins
• part of the outer cell wall of Gram (-)
bacteria. ??
Exotoxins versus Endotoxins
 I- Exotoxins
◗ Mostly seen in Gram (+) Bacteria

◗ Most gene that code for exotoxins are

located on plasmids or phages
Three Types of Exotoxins
◗ 1. Cytotoxins
• kill cells e.g. Diphtheria toxin
◗ 2. Neurotoxins
• interfere with normal nerve impulses.e.g.
Botulinum Toxin
◗ 3. Enterotoxins
• effect cells lining the G.I. Tract. e.g. Cholera
toxin or choleragen.
Response to Toxins
◗ If exposed to exotoxins: antibodies against the
toxin (antitoxins)
◗ Exotoxins inactivated ( heat, formalin or phenol)
no longer cause disease, but stimulate the
production of antitoxin
• altered exotoxins - Toxoids
◗ Toxoids - modified toxin by heat, chemical,
radiation, that have lost their toxicity. Injected to
stimulate the production of antitoxins and provide
immunity.
Example: DPT Vaccine
◗ D - Diphtheria
• Corynebacterium diphtheriae
◗ P - Pertussis
• Bordetello pertussis
◗ T - Tetanus
• Clostridium tetani
DPT - Diphtheria Toxoid
Pertussis Antigen
Tetanus Toxoid
 Required Immunizations
◗ 1. Diphtheria ◗ Corynebacterium diphtheriae
◗ 2. Pertussis ◗ Bordetello pertussis
◗ 3. Tetanus ◗ Clostridium tetani
◗ 4. Measles ◗ Measles virus
◗ 5. Mumps ◗ Mumps virus
◗ 6. Rubella ◗ Rubella virus
• German Measles
◗ 7. Polio ◗ Polio virus
◗ 9. Hepatitis B ◗ Hepatitis B Virus
 Most genes that code for exotoxins - plasmids
or phages
◗ Lysogenic convergence
◗ Diphtheria
◗ Cytotoxin inhibits
protein synthesis -
resulting in cell death
◗ Pseudomembrane
• fibrin, dead tissue,
bacterial cells
Lysogenic Convergence
◗ Scarlet Fever
◗ Streptococcus pyogenes
• lysogenic convergence
◗ cytotoxin - damages blood capillaries and results in a
skin rash
• Strep Thoat with a rash
Rash of Scarlet Fever Caused by
Erythrogenic Toxins of Streptococcus
pyogenes
Diseases Caused by Staphylococcal Toxins

Scalded Skin Syndrome Toxic Shock Syndrome

Diseases caused by Neurotoxins
◗ Botulism
• Clostridium botulinum
• Gram (+), anaerobic, spore-forming rod, found in
soil
• works at the neuromuscular junction
• prevents impulse from nerve cell to muscle cell
• results in muscle paralysis
Tetanus (Lock Jaw)
◗ Clostridium tetani
◗ Gram (+), spore-forming, anaerobic rod
◗ neurotoxin acts on nerves, resulting in the
inhibition of muscle relaxation
◗ tetanospasmin - “spasms” or “Lock Jaw”
 Muscle Spasms of Tetanus are Caused by
Neurotoxin of Clostridium tetani

Neonatal Tetanus (Wrinkled brow and risus sardonicus)

Source: Color Guide to Infectious Diseases, 1992
Diseases caused by Enterotoxins
◗ Cholera
• Vibrio cholerae
• Gram (-) comma
shaped rods
 Cholera toxin

◗ Converts ATP into cAMP

◗ causes cells to excrete Cl- ions and inhibits
absorption of Na+ ions
◗ Electrolyte imbalance
◗ H2O leaves by osmosis
◗ H2O Loss (Diarrhea)
◗ Two polypeptides: A (active) and B (binding).
The A subunit of enterotoxin causes epithelial
cells to discharge large amounts of fluids and
electrolytes.
 Severe cases, 12 - 20 liters of liquid lost
in a day
◗ Untreated cases - Mortality Rate about 50%

◗ Mortality may be reduced to about 1%

• administering fluids and electrolytes
Vibrio Enterotoxin Causes Profuse Watery Diarrhea

Rice-water stool of cholera. The A subunit of enterotoxin causes

epithelial cells to discharge large amounts of fluids and electrolytes.
Source: Tropical Medicine and Parasitology, 1995
EHEC (Enterohemorrhagic E. coli)
◗ E. coli (0157:H7)
◗ enterotoxin causes a hemolytic inflammation
of the intestines
◗ results in bloody diarrhea
• Toxin
• alters the 60S ribosomal subunit
• inhibits Protein Synthesis
• Results in cell death
• lining of intestine is “shed”
• Bloody Diarrhea (Dysentary)
More on Toxins
 II- Endotoxins
• Part of outer membrane surrounding gram-negative
bacteria.
• Endotoxin is lipid portion of lipopolysaccharides (LPS),
called lipid A.
• Effect exerted when gram-negative cells die and cell
walls undergo lysis, liberating endotoxin.
• All produce the same signs and symptoms:
• Chills, fever, weakness, general aches, blood clotting
and tissue death, shock, and even death. Can also
induce miscarriage.
• Fever: Pyrogenic response is caused by endotoxins.
Exotoxins vs. Endotoxins
Endotoxin is LPS
 Endotoxins (Continued)
• Endotoxins do not promote the formation of
effective antibodies.
• Organisms that produce endotoxins include:
• Salmonella typhi
• Proteus spp.
• Pseudomonas spp.
• Neisseria spp.
• Medical equipment that has been sterilized may
still contain endotoxins.
• Limulus amoebocyte assay (LAL) is a test used to
detect tiny amounts of endotoxin.
 Events leading to fever:
• Gram-negative bacteria are digested by
phagocytes.
• LPS is released by digestion in vacuoles, causing
macrophages to release interleukin-1 (IL-1).
• IL-1 is carried via blood to hypothalamus, which
controls body temperature.
• IL-1 induces hypothalamus to release
prostaglandins, which reset the body’s
thermostat to higher temperature.
Microbial Mechanisms of Pathogenicity:
How Microorganisms Cause Disease
 III. B. The Normal Flora of
Humans
◗ Types of Symbiosis
• Mutualism
• A symbiotic relationship in which both
species benefit
• Commensalism
• A symbiotic relationship in which one
species benefits, and the other species is
neither helped nor harmed
 III. B. The Normal Flora of
Humans
◗ Types of Symbiosis (cont.)
• Parasitism
• A symbiotic relationship in which one
species benefits, and the other species is
harmed
• Generally, the species that benefits (the
parasite) is much smaller than the species
that is harmed (the host)
 III. B. The Normal Flora of
Humans
◗ Normal flora is present in
• skin
• upper respiratory tract
• oral cavity
• intestine, especially large intestine
• vaginal tract
◗ Very little normal flora in eyes & stomach
 III. B. The Normal Flora of
Humans
◗ Notably absent in most all internal organs
• Absent in:
• lower respiratory tract
• muscle tissue
• blood & tissue fluid
• cerebrospinal fluid
• peritoneum
• pericardium
• meninges
 III. B. The Normal Flora of
Humans

◗ Benefits of the normal flora

• Nutrient production/processing
eg Vitamin K production by E. coli
• Competition with pathogenic microbes
• Normal development of the immune system
◗ Normal flora and opportunistic infections
 III. C. Generalized Stages of
Infection
1. Entry of Pathogen
• Portal of Entry
2. Colonization
• Usually at the site of entry
3. Incubation Period
• Asymptomatic period
• Between the initial contact with the microbe
and the appearance of the first symptoms
 III. C. Generalized Stages of
Infection
4. Prodromal Symptoms
• Initial Symptoms
5. Invasive period
• Increasing Severity of Symptoms
• Fever
• Inflammation and Swelling
• Tissue Damage
• Infection May Spread to Other Sites
III. C. Generalized Stages of
Infection

6. Decline of Infection

5. Convalescence
Course of Infectious Disease

Convalescence is
a time of
recuperation and
recovery from
illness.

Depending on various
Incubation period is factors an individual may
the interval between still be infectious during
exposure and either incubation or
illness onset. convalescence.