Bacterial

Pathogenicity
Dr. N.P. Senanayake
KDU
05/09/2016
 Outline
Bacterial Pathogenesis

Introduction

Host Susceptibility

Pathogenic
Mechanisms

Virulence Factors
 Introduction
Microorganisms (viruses, bacteria, fungi
and protozoans) are closely associated
with human hosts.
All host-microbe associations are not
pathogenic

Many factors can influence this association

Virulence
Site
Immune status of host
 Host Parasite relationship
One species living in or on the body of
another
This association is called Symbiotic
association
Can be harmless, or harmful
Usually on body surfaces skin, mucosa
3 categories of associations
1. Commensalism
2. Mutualism
Saphrophyte
3. Parasitism
Free living organisms found in
soil & decaying vegetations
 Commensalism
Microorganism may use a body of a larger
species for food and shelter
Normally does not cause harm to the host
normal flora / commensals
But can be harmful if environmental conditions change
( E. coli in urinary tract)
Opportunistic pathogens
Commensals can benefit the host
Intestinal organisms can prevent colonizing pathogens
(Bacteroides spp)
Can produce metabolites which can be used by the
host
 Mutualism
Benefit both the host and the micro organism
Prevent colonization of pathogens on mucosal surfaces
Bacteria in ruminants (cattle, sheeps) intestines that
digest cellulose

Parasitism
Harmful to the host
Benefit only the micro organism
Rabies virus
 Symbiotic association
Benefit only
Disease one species

Parasitism

Commensalism Mutualism

No harm to the Benefit both

host species
 Introduction
Infection: growth and multiplication of a microbe in
or on the body with or without the production of
disease.

Pathogenicity: The capacity of a bacterium to

initiate disease.

Pathogenesis refers both to the mechanism of

infection and to the mechanism by which disease
develops.
 Introduction
Infection occurs when imbalance between
The capacity of the microorganism to
multiply, spread and cause disease and
The ability of the host to control and
stop the infection
Innate and specific immune responses
General health of the host & age

Early host response Delayed host

no infection response - disease
 Frequency of clinically
apparent disease
There is variation in severity of clinical disease

In some infections all or majority infected will

have clinical disease
Eg. Rabies, smallpox

But in other infections,

majority may have mild or asymptomatic infection and
Only a minority of infected will have clinical disease
Eg. Polio (~ 1% have clinical disease), Dengue

This is called iceberg phenomenon

Iceberg concept of infectious
disease

Less severe
disease

Asymptomatic
Infection,

Can infect others

 Introduction
Pathogenicity requires the attributes of,

Transmissibility (ability to move from one host or

reservoir to another host)
Survival (in the new host)
Infectivity (ability to breech the new host
defences)
Virulence (capacity of the pathogen to harm the
host)
 Host susceptibility
Susceptibility to bacterial infections
=> Host Defenses vs Bacterial Virulence

Host Defenses:
- Barriers (skin & mucus) first line
- Innate Immune Responses (complement, macrophages &
cytokines) the early stage
- Adaptive Immune Responses (Ag-specific B & T cells) the
later stage

Host defenses can be comprised by destructing barriers or

defective immune response.
 Types of bacterial pathogens
Primary pathogens: Capable of establishing
infection and causing disease in previously
healthy individuals with intact immunological
defences.

Opportunistic pathogens: Rarely causes

diseases in previously healthy individuals, but
causes diseases with immunological defences.
Characteristics of pathogenic
bacteria
Establishment of infection
(source, route of entry,
transmission)
Adherence to host cells
Invasion of host cells and
tissue
Evasion of the host
immune system
Toxigenicity
 Source of infection

Patients (clinical disease or

subclinical infections, infected
carriers)

Normal commensal flora

Inanimate objects

Environmental (water, food, air

etc.)
 Entry into the human body
The most frequent portals of
entry- Mucus
- Skin

Routes:
Ingestion, inhalation,
trauma, needles, catheters,
arthropod bite, sexual
transmission
 Transmission of infection

Direct contact: from one

person to another person

Indirect contact:
- ingestion of
contaminated food and
water
- air borne particles
- via animals and insects
 Pathological mechanisms of
bacterial infections

Bacteria-mediated Pathogenesis
Host-mediated Pathogenesis
Bacterial virulence factors

=> bacterial factors causing diseases

Bacterial virulence mechanisms
 Bacterial virulence factors
Adhesins
Pili (fimbriae)
Nonfimbrial adhesins
Invasion of host cells
Tissue damage
Growth byproducts
Tissue-degrading enzymes
Immunopathogenesis
Toxins
Exotoxins(cytolytic enzymes & A-B toxins),enterotoxins
Superantigens
Endotoxins and other cell wall components
 Bacterial virulence factors
Anti-phagocytic factors
Intracellular survival
Antigenic heterogeneity
Antigenic variation
Phase variation
Iron acquisition
Siderophores
Receptors for
iron-containing molecules
Resistance to antibiotics
 Adhesion
Adherence of bacterium
to epithelial or
endothelial cells allow
them to colonize the
tissue.

Common adhesins: pili

(fimbriae), slime,
lipoteichoic acid, surface
proteins or lectins.
 Adhesion
Adhesion enables the establishment of a stable
population of bacteria in the host.

Adhesion is necessary:

- to avoid host defence mechanisms and antibiotics

- penetrate through tissues (invasive bacteria)

- acquire essential nutrients

 Adhesion
Biofilm, formed on a surface
by the bacteria that are bound
together within a sticky web of
polysaccharide, is a special
bacterial adaptation .

It facilitates colonization on the

surgical appliances (e.g.,
artificial valves or indwelling
catheters) and dental plaque. It
can protect the bacteria from
host defenses and antibiotics.
 Invasion
Ability of a pathogen to invade tissues.

The invasion of a host by a pathogen may

be aided by the production of bacterial
extracellular substances (invasins) which
act against the host by breaking down
primary or secondary defenses of the
body.
 Invasion
Most invasins are
proteins (enzymes)
that act locally to
damage host cells
and/or have the
immediate effect of
facilitating the
growth and spread
of the pathogen.
 Bacterial invasins
Spreading factors - hyaluronidase, neuraminidase,
collagenase, streptokinase, staphylokinase

Enzymes causing haemolysis and leukolysis-

phospholipase, lecithinase, haemplysins

Staphylococcal coagulase

Extracellular digestive enzymes

 Intracellular pathogens
Some organisms
are able to invade
and survive within
host cells.

eg. Mycobacteria,
Salmonella, Shigella,
Escherichia,
Legionella, Listera,
Yersinis, Neiseria
Evasion of the host immune system

Colonization by bacterial pathogens

result in the induction of the specific
and the non-specific humoral and
cellular immune responses.

Pathogenic bacteria have evolved ways of

avoiding or neutralizing these highly
efficient immune mechanisms.
Evasion of the host immune system
Encapsulation (Inhibition of phagocytosis and serum
bactericidal effect)
Antigenic mimicry
Antigenic masking
Antigenic or phase variation
Intracellular multiplication
Escape phagosome
Inhibition of phagolysosome fusion
Resistance to lysosomal enzymes
Production of anti-immunoglobulin protease
Inhibition of chemotaxis
Destruction of phagocytes
Mechanisms for escaping phagocytic
clearance and intra-cellular survival
Mechanisms for escaping phagocytic
clearance and intra-cellular survival
 Toxigenicity
In many bacterial infections the characteristic
pathology of the disease is caused by toxins.

Toxins may exert their pathogenic effects

directly on a target cell or may interact with
the cells of the immune system resulting in the
release of immunological mediators (cytokines)
that cause pathophysiological effects,
 Types of toxins

Endotoxins - component
of the outer membrane of
Gram negative bacteria

Exotoxins - produced
extra-cellularly by both
Gram negative and
Gram positive bacteria
 Endotoxin
Also called LPS (lipopolysaccharide) is a
component of the outer membrane of
the Gram negative bacteria.

Released from the bacterial surface via

outer membrane vesicles, following
natural lysis of the bacterium or by
disintegration of the organism.
 Endotoxin
Most of the biological activity of the
molecule is attributable to Lipid A.

Both endotoxin and Lipid A are potent

activators of macrophages, resulting in
the induction of a range of cytokines
which are involved in the induction of range
of immune and inflammatory responses.
 Endotoxin
Pathogenesis of sepsis (septicemia)

Endotoxin mediated toxicity

Fever
leukopenia followed by leukocytosis
activation of complement, thrombocytopenia
disseminated intra-vascular coagulation
decreased peripheral circulation and perfusion to major
organs (multiple organ system failure)
Shock and death.
 Super antigen mediated toxicity
Bind to TCR and
activate T cells
Autoimmune-like
responses
S. aureus =>Toxic shock
syndrome toxin
S. pyogenes=> Erythrogenic
toxin A orC
 Exotoxin
Diffusible proteins
secreted into the
external medium by
the pathogen.

o Exotoxins facilitate -
adhesion to and
invasion of the host,
damage to host cells
 Exotoxin
A chain has the inhibitory activity against some vital
function
B chain binds to a receptor and promotes entry of the A
chain

Mode of action
Inhibition of protein synthesis
Hypersecretion
Inhibition of neurotransmitter release
In many cases the toxin gene is encoded on a plasmid or a
lysogenic phage
 Exotoxin
Lethal action - botulinum,
tetanus, dlphtheria toxin
Pyrogenic effect - S.aureus
toxin
Action on GIT - Cholera and
E.coli enterotoxin
Cytolytic effect -
C.perfringens (gas
gangrene)
Inhibition of protein
synthesis - Diphtheria
toxin
Regulation of bacterial virulence factors

Environmental factors often control the

expression of the virulence genes.

Common factors: temperature, iron availability,

osmolarity, growth phase, pH, specific ions,
specific nutrient factors, bacterial cell-density,
interaction with host cells.
 Robert Koch

In 1890 Robert Koch

came out with a set
of rules to show
that specific micro
organism cause a
specific disease
 Robert Koch
This was important in early microbiology
because germ theory association of
microorganisms with disease was new in
1890s

Koch was the first to culture bacteria in the lab

on potatoes
In 1876 isolated Anthrax bacillus
In 1882 Mycobacterium tuberculosis
In 1883 Vibrio cholerae
 Kochs Postulates
1. Microbe must be present in every case of
disease
2. Microbe must be isolated from the diseased host
and grown in pure culture
3. The disease must be reproduced when pure
culture is given to a another host
4. The microbe must be recovered from the second
host

However, these rules will not be always useful

Serological diagnosis
Some organisms can not be cultured T. pallidum
 Further reading

Medical Microbiology - David Greenwood

- 17th edition
- Chapter thirteen
 Thank you