Dr.

Mejbah Uddin Ahmed

 Bacterial Pathogenesis

Bacterial pathogens are of two types:

a) Primary pathogen: Are capable of
establishing infection and causing disease in
previously healthy individuals.
b)Opportunistic pathogens: Are capable of
establishing infection and causing disease in
immunocompromised individuals.
 Bacterial Pathogenesis

Virulence: Is a measure of a microbe’s ability

to cause disease. Both primary and
opportunistic pathogens possesses several
virulence factors that facilitate pathogenesis.
Pathogenesis
Virulence Factors:
●Adhesins: Pili or fimbria, teichoic acid, M protein,
haemaglutinin, Curli protein, slime layer, capsule.
● several enzymes: Coagulase, hyaluronidase,
collagenase, IgA protease etc.
● Toxins.
● Antigenic variation.
● Anti phagocytic activity.
● Intracellular survival.
 Pathogenesis

Steps of bacterial Pathogenesis: Generalized

sequences of events of infection are as
follows:
A) Transmission ( when normal flora cause
disease does not need transmission).
B) Evasion of primary host defense e.g. skin,
mucous membrane, stomach acid etc.
C) Adherence at the site of infection.
 Pathogenesis

Steps of bacterial Pathogenesis:

D) Colonization and growth at that side.
E) Disease production by toxin or invasion
and inflammation.
F) Host response/Immune response.
G) Progression or resolution of disease.
 Steps of pathogenesis
A) Transmission:
1) Human to human transmission
a) Direct contact.
b) No direct contact.
c) Vertical.
d) Blood borne.
a) Direct contact: Intimate close contact; e.g.
sexual: Gonorrhea.
b) No direct contact: Through airborne
respiratory droplets, fecal contamination of
food and water, fomites etc.
 Steps of pathogenesis

c) Vertical transmission:
From mother to fetus during intrauterine and
perinatal life.
•Transplacental: Treponema pallidum,
Listeria monocytogens.
•Within birth canal: Streptococcus agalactiae,
Esch. Coli, Chlamydia, N. gonorrhoeae.
•Breast milk: Staph. Aureus.
 Steps of pathogenesis

d) Blood borne: During blood transfusion or

intravenous drug use: Syphilis.
2) Nonhuman to human:
a) Soil: Spore of clostridium causes wound
infection.
b) Water: V. cholerae, Salmonella, L. pneumophia.
c)Food: Salmonella, Clostridium botulinum.
d) Animal source (zoonotic).
 Pathogenesis
d) Animal source (zoonotic):

Bacterium Reservoir Disease

B. anthrcis Domestic Anthrax
animals
Yersinia Domestic animals, Diarrhea, sepsis
Rodents

Leptospira Rat and dog Leptospirosis

Rickettsia Rat and dog Rocky mounted spotted
fever
 Steps of pathogenesis

Adhesion : Several structures are involved in

adhesion by the interactions between specific
receptors on the host tissue and ligands on
the bacterial surface.
 Steps of pathogenesis
Colonization: Successful colonization is also
require to acquire essential nutrients for
growth.
B)Immune evasion: Once colonize,
pathogenic bacteria are able to evade host
immune response by avoiding or
neutralizing these highly efficient clearance
systems.
 Pathogenesis

Following structures and mechanisms are

involved in immune evasion:
Antiphagocytic action:
●Capsule: Capsule inhibits phagocytosis by
preventing interaction between antibody and C3
bound to outer membrane of bacteria and their
receptors.
 Pathogenesis

●Antigenic variation:
Variation occurs in surface antigen during the
course of infection and helps in avoidance of
specific immune response directed at those
antigens e.g. N. meningitidis.
 Pathogenesis

● IgA protease:
Several bacteria produces protease enzyme
that specifically cleaves secretory IgA and
helps the bacteria to persist them on he
mucosal surface and resist phagocytosis.
 Pathogenesis

● Serum resistance:
To survive in the bloodstream some
bacteria are able to resist complement
mediated lysis. Which possess “O” side
chain in their LPS are more resistant.
 Pathogenesis
●Intracellular survival after
phagocytosis by following
mechanisms:
1)Inhibition of the fusion of phagosome
with lysosome by “exported repetitive
protein”: e.g. Mycobacterium.
 Pathogenesis

2)Inhibition of acidification of the

phagosome which reduces the activity of
lysosyme e.g. legionella.
3)Escape from phagosome into the
cytoplasm e.g. Listeria.
 Pathogenesis
C) Disease production by toxins, enzyme,
invasion and inflammation:
Toxins: Are either bacterial part or bacterial
production, cause damage to host tissue or may
interact with immune system and cause
pathological effect.
Two major types of toxins:
a) Endotoxin
b) Exotoxin.
 Pathogenesis

Endotoxin: LPS or LOS, of the outer membrane

components of Gram-negative bacteria.
They are released after lysis of bacterial cell in
vitro.
Cause activation of macrophages and
complement via alternative pathway.
Results in release of cytokines and exert their
biological effect.
 Pathogenesis

Biological effects of endotoxin:

•Activates Macrophage:
IL-1 → fever.
TNF → Fever and hypotension.
Nitric oxide → Hypotension.
 Pathogenesis

Biological effects of endotoxin:

• Activates complement →
C3a → Hypotension, edema.
C5a → Neutrophil, chemotaxis.
• Activates Hagement factor (XII) →
Coagulation cascade →DIC.
 Pathogenesis

• Exotoxin: Exotoxins are diffusible proteins

secreted by bacteria.
• Vary in their molecular structures,
mechanism of secretion, biological function
and immunological properties.
 Pathogenesis
Features of Endotoxin & Exotoxin:
Property Exotoxin Endotoxin

Source Gram-positive& Gram-negative

Gram-negative
Chemistry Polypeptide LPS

Location of genePlasmid Bacterial

/bacteriophage chromosome
Toxicity High(1μg is fatal) Low(100 μg fatal)
 Property Exotoxin Endotoxin

Clinical effect Various Fever, shock, DIC

Mode of action Various TNF, IL-1

Antigenicity High Poor

Vaccine Toxoids used in No

vaccine
Heat stability Destroyed at Stable at 100ºC
60ºC
 Pathogenesis
Mechanism of action of important exotoxins:
Mechanism of action Exotoxin

ADP ribosilation Diphtheria toxin, cholera

toxin, pertussis toxin etc.

Super antigen TSST, Staph. enterotoxin

Protease Tetanus, Botulinum toxin,

Anthrax toxin.
Lecithinase Cl. Perfringes alpha toxin.
 Pathogenesis

• Several important exotoxin:

• Bacillus anthracis (Anthrax toxin):
Edema Factor→ An adenylate cyclase → causes
↑ed level of cyclic AMP in phagocytes → ion-
permeable pores in membranes.
Lethal factor: Protease → cleaves phosphokinase,
required for growth of cells.
Protective antigen: Binds to cell surface.
 Pathogenesis
• Bordetella pertussis toxin:
Stimulates adenylate cyclase activity → causes
↑ed levels of CAMP →causes edema and also
inhibits chemokine receptor.
• Corynebacterium diphtheriae(Diphtheria
toxin):
ADP ribosylation of elongation factor-2 leads to
inhibition of protein synthesis in target cells.
 Pathogenesis
• Vibrio cholerae(Cholera enterotoxin):

ADP ribosylation of G proteins→stimulates

adenylate cyclase→increases cAMP
→causes secretion of water and electrolytes.
• Staph. Aureus (Toxic shock syndrome toxin):
Acts on the vascular system causing fever,
shock and inflammation.
 Pathogenesis
• Clostridium botulinum(Botulinum toxin):

Protease that degrade protein responsible for

release of acetylcholine at neuromuscular
synapses resulting in flaccid paralysis
• Clostridium tetani(Tetanus toxin):
Protease that inhibits release of inhibitory
neurotransmitter glycine resulting in spastic
type paralysis.
 Pathogenesis
• Staphylococcus aureus(enterotoxin):
Causes release of cytokines from lymphoid
cells→stimulates enteric nervous system →
activates vomiting center.
• Shigella dysenteriae(Shiga toxin):
Enzymatically cleaves rRNA resulting in
inhibition of protein synthesis in susceptible
cells.
 Pathogenesis

Disease production by enzymes:

Several enzymes secreted by bacteria play
role in the pathogenesis e.g. collgenase,
hyaluronidase, coagulase, protease,
leukocidin, Streptokinase, DNAase etc.
 Pathogenesis
Important water borne diseases:
•Ingestion of drinking water: Salmonella,
Shigella, Campylobacter, E. coli, Vibrio
cholerae.
•Ingestion of water while swimming:
Leptospira interrogans.
• Inhalation of water aerosol: Legionella
pneumophila.