1. Bacterial Pathogenesis
Pin Ling (凌 斌), Ph.D.
Department of Microbiology & Immunology, NCKU
ext 5632
References:
1. Chapter 19 in Medical Microbiology (Murray, P. R. et al; 5th edition)
2. 醫用微生物學 (王聖予 等編譯, 4th edition)

2. Outline Bacterial Pathogenesis Introduction Host Susceptibility
Pathogenic Mechanisms
Virulence Factors

3. Introduction of Bacterial Pathogenesis
Infection: growth and multiplication of a microbe in or on the body with or without the production of disease.
The capacity of a bacterium to cause disease reflects its relative “Pathogenicity.”
3. Virulence is the measure of the pathogenicity of a microorganism.
4. Pathogenesis refers both to the mechanism of infection and to the mechanism by which disease develops.

4. 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.
e.x. Cystic Fibrosis => poor ciliary function => NOT clear mucus efficiently from the respiratory tract => Pseudomonas aeruginosa => serious respiratory distress.

5. Strict pathogens are more virulent and can cause diseases in a normal person.
Opportunistic pathogens are typically members of normal flora and cause diseases when they are introduced into unprotected sites, usually occur in people with underlying conditions.

6. Entry into the human body
The most frequent portals of entry- Mucus
- Skin
Routes:
Ingestion, inhalation, trauma, needles, catheters, arthropod bite, sexual transmission
: infection
: shedding

7. Characteristics of Pathogenic Bacteria
Transmissibility
Adherence to host cells
3. Invasion of host cells and tissue
Evasion of the host immune system
Toxigenicity
A bacterium may cause diseases by
Destroying tissue (invasiveness)
Producing toxins (toxigenicity)
Stimulating overwhelming host immune responses

8. Pathological Mechanisms of Bacterial Infections
Bacteria-mediated Pathogenesis
Host-mediated Pathogenesis
Bacterial virulence factors
=> bacterial factors causing diseases
Adopted from Samuel Baron “Medical Microbiology”

9. Bacterial Virulence Mechanisms

10. Bacterial virulence factors
Adhesins
Pili (fimbriae)
Nonfimbrial adhesins
Invasion of host cells
Tissue damage
Growth byproducts
Tissue-degrading enzymes
Immunopathogenesis
Toxins
Exotoxins (cytolytic enzymes and A-B toxins); enterotoxins;
superantigens;
endotoxin and other cell wall components
Antiphagocytic factors
Intracellular survival
Antigenic heterogeneity
Antigenic variation
Phase variation
Iron acquisition
Siderophores
Receptors for
iron-containing molecules
Resistance to antibiotics

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

12. The bacteria may invade via the M cells
M (Microfold) cells
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13. Endotoxin (LPS)-mediated toxicity
Lipid A of lipopolysaccharide is responsible for endotoxin activity
Pathogenesis of sepsis (septicemia)

14. Endotoxin-mediated toxicity
Fever,
leukopenia followed by leukocytosis,
activation of complement, thrombocytopenia,
disseminated intravasacular coagulation,
decreased peripheral circulation and perfusion to major organs (multiple organ system failure),
Shock and death.
Peptidoglycan, teichoic and lipoteichoic acids of gram-positive bacteria stimulate pyrogenic acute phase responses and produce endotoxin-like toxicity
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15. Superantigen-mediated toxicity
1. Bind to TCR and activate T cells w/o Ag
2. Autoimmune-like responses
3. S. aureus =>Toxic shock syndrome toxin
S. pyogenes=> Erythrogenic toxin A orC
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16. The A-B toxins
A chain has the inhibitory activity against some vital function
B chain binds to a receptor and promotes entry of the A chain
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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

17. Microbial defenses against host immunologic clearance
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

18. Mechanisms for escaping phagocytic clearance and intracellular survival

19. Mechanisms for escaping phagocytic clearance and intracellular survival

20. Mechanisms for escaping phagocytic clearance and intracellular survival

21. 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.

22. SUMMARY 1. 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
2. Susceptibility to bacterial infections depends on the balance between host defenses and bacterial virulence.
3. Pathogenic mechanisms of bacterial infections include
Bacteria-mediated Pathogenesis
Host-mediated Pathogenesis

24. Mechanisms of acquiring bacterial
virulence genes