mechanism of pathogenisity\

1. Microbial Mechanisms of
Pathogenicity

2. How Pathogens Damage Host Cells
1. Use host’s nutrients
2. Cause direct damage
3. Produce toxins
4. Induce hypersensitivity reaction

3. Determinants of Pathogenesis
1. Transmission
2. Adherence and invasion
3. Enzymes
4. Toxin production
5. Immunopathogenesis

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• Surface projections on pathogen, mostly made of
glycoproteins or lipoproteins.
• Adhere to complementary receptors on the host
cells.
Adhesins can be part of:
Adherence
 Glycocalyx
 Fimbriae
 Capsule
 Pilli
 flagella

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 Capsules:
- increase the virulence of organism
- resist host defenses by impairing phagocytosis
- prevent phagocytic cell adherence to organism
- many non pathogens produce capsule, virulence of some pathogen not
related to the presence of capsule
- S.pneumoniae, K.pneumonia, H.influenzae

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 Coagulase: Blood clot formation. Protection from phagocytosis
 Kinase: blood clot dissolve (e.g.: streptokinase)
 Hyaluronidase: (Spreading factor) Digestion of “intercellular
cement”  tissue penetration
 Collagenase: Collagen hydrolysis
 IgA protease: IgA destruction
 Leukocidins: destroy neutrophils leukocytes and macrophages
 DNAse: degrade DNA in necrotic tissue
Enzymes

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Enzymes Used for Penetration

9. Cell Wall Proteins:
 Antiphagocytic factor (resist phagocytosis)
 heat resistant and acid resistant protein e.g. M protein of S. pyogenes.
 found both on cell surface and fimbriae
 N.gonorrhoeae use fimbriae and outer membrane protein (Opa)
 Following attachment host cell take in bacteria
 mycoloic acid in M.tuberculosis resist digestion by phagocytosis

10. • Antigenic Variation:
Neisseria
• Penetration into the Host Cell Cytoskeleton: Salmonella and E. coli
produce invasins, proteins that cause the actin of the host cell’s
cytoskeleton to form a basket that carries the bacteria into the cell.

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 Invasins
 Salmonella alters
host actin to enter
a host cell
 Use actin to move
from one cell to the
next
 Listeria
Penetration into the Host Cell Cytoskeleton

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Toxins
Exotoxins: proteins (Gram negative and
Gram positive bacteria)
Endotoxins: Gram -ve bacteria only.
LPS, Lipid A part  released upon cell
death. Symptoms due to vigorous
inflammation. Massive release 
endotoxic shock

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Exotoxins Summary
Source: Gram +ve and Gram -ve
Relation to microbe: By-products of growing cell
Chemistry: Protein
Fever? No
Neutralized by antitoxin? Yes
LD50: Small
Circulate to site of activity. Affect body before immune response
possible.
Exotoxins with special action sites: Neuro-, and enterotoxins

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Membrane-Disrupting Toxins
Lyse host’s cells by
1. Making protein channels into the plasma membrane, e.g.
S. aureus
2. Disrupting phospholipid bilayer, e.g. C. perfringens
Examples:
Leukocidin
Hemolysin

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Superantigens
• Special type of Exotoxin
• Nonspecifically stimulate T-cells
• TSST also known as T-cell mitogen i.e it induce T-cells to
multiply which contributes to the overproduction of cytokines
• Cause intense immune response due to release of cytokines
from host cells.
• Fever, nausea, vomiting, diarrhea, shock and death
• Example-TSST, staphylococcal enterotoxin, erythrogenic
toxin

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Bacterial Species Exotoxin Lysogeny
C. diphtheriae A-B toxin +
S. pyogenes
Membrane-disrupting
erythrogenic toxin
+
C. botulinum A-B toxin; neurotoxin +
C. tetani A-B toxin; neurotoxin
V. cholerae A-B toxin; enterotoxin +
S. aureus Superantigen +
Representative Examples of Exotoxins

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Endotoxins
 Bacterial cell death, antibiotics, and antibodies may cause the
release of endotoxins.
 Endotoxins cause fever (by inducing the release of interleukin-1)
and shock (because of a TNF-induced decrease in blood
pressure).
 TNF release also allows bacteria to cross blood brain barrier.

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Source: Gram –
Relation to
microbe:
Present in LPS of outer
membrane
Chemistry: Lipid A component of LPS
Fever? Yes
Neutralized by
antitoxin? No
LD50: Relatively large
Endotoxin Summary

19. Immunopathogenesis
• The mechanisms whereby disease is caused by immune
response against antigens not due the presence of antigen
itself
• e.g in rheumatic fever, antibodies are formed against M
protein of St.pyogenes which cross react with joint, heart and
brain tissues
• Results in arthritis, carditis

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Microbial Mechanisms of Pathogenicity
Overview