1. Host Defenses, Microbial Evasion & Virulence Factors

2. Overview Host Defenses Microbial Virulence Factors
Host Evasion Tactics

3. ** Host Defenses **No bacteria can penetrate intact skin
Bacteria vs Antibacterial Agents 2003 Mascaretti OA (editor)
**No bacteria can penetrate intact skin

4. Toll-like receptors: Innate immune system
Pattern recognition receptors (PRR); produce lymphokines when stimulated
Microbial Pathogenesis and the Intestinal Epithelial Cell 2003 Hecht GA (Editor)

5. Classes of Lymphocytes
Antigen recognition Effector functions
Antibody Secretion
B lymphocyte
Activation of B & T cells
Macrophage activation
Helper T lymphocyte (CD4)
Inflammation
Target cell lysis
Cytolytic T lymphocyte (CTL) (CD8)
Target cell lysis
Natural Killer cell (NK)
Bacteria vs Antibacterial Agents MascarettiOA (ed) 2003

6. Superantigens
- S.pyogenes
- S.aureus

7. Macrophage & Epithelial cells
Pathogen
Disease
Host cell Interaction
Extracellular:
S.aureus
S.pneumoniae
B. pertussis
N. gonorrhoeae
E.coli
H.pylori
Skin/Tissue
Pneumonia
Whooping cough
Gonorrhea
UTI, diarrheas, meningitis
Ulcers, gastritis
Adherence to ECM
Adherence to cells
Intracellular
Macrophages:
L. pneumoniae
M. tuberculosis
Macrophage & Epithelial cells
Salmonella species
Shigella species
L.monocytogenes
Chlamydia species
Legionaires’ disease
Tuberculosis
Typhoid fever, gastroenteritis
Dysentery, gastroenteritis
Listeriosis, meningitis
Trachoma, STD, pneumonia
Within vacuole
Intracytoplasmic

8. Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Prokaryotic Cell
Pili or adhesins
Intracellular
Control of virulence factors: (Pilin, capsule, invasins, toxins etc)
Virulent Bacteria
Adherence blockers
Receptor

9. Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Prokaryotic Cell
Pili or adhesins
Intracellular
Control of virulence factors: (Pilin, capsule, invasins, toxins etc)
Virulent Bacteria
Adherence blockers
Receptor
COLONIZATION

10. Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Prokaryotic Cell
Pili or adhesins
Intracellular
Control of virulence factors: (Pilin, capsule, invasins, toxins etc)
Virulent Bacteria
Adherence blockers
Receptor
COLONIZATION
INVASION

11. Bacterial Invasion: Conserved macromolecular systems
Adherence (attachment)
Entry into body
Avoidance of host immune defense
Damage (tissue or functionality)
Resist antibacterial agents

12. Adhesion Pilus: Chaperone-usher pathway - E.coli
Non-pilus Adhesins - invasin (Y.pseudotuberculosis) - intimin (enteropathogenic E.coli)

13. Pilus tip Fibrillum subunits Pilus assembly machinery
Chaperone-Usher Pathway
Adhesin: binds Gal(α1-4)Gal A A
Tip Fibrillum A A
Pilus Shaft A A
Usher C H C
Gm(-) Bacterial Periplasm A
Cytoplasmic membrane A H A D
Chaperone
Pilus tip Fibrillum subunits
Pilus assembly machinery
Pilus subunit I B A H C D J K E F G
Regulation
Anchor
Usher
Chaperone

14. Intimin (Enteropathogenic E.coli)
Nonpilus Adhesin
Intimin (Enteropathogenic E.coli)
Microbial Pathogenesis and the Intestinal Epithelial Cell 2003 Hecht GA (Editor)

15. Toxins Listeriolysin O Superantigens: e.g. Spe, TSST1
Bacteria vs Antibacterial Agents 2003 Mascaretti OA (editor)

16. Exotoxins: Proteins Clostridium tetani; Tetanus toxin (neurotoxin)
Clostridium botulinum; Botulinum toxin (neurotoxin)
Clostridium perfringens: Clostidial toxin (phospholipase activation)
Clostridium difficile; Toxin A (enterotoxin), Toxin B (cytotoxin)
Streptococcus pyogenes; Erythrogenic toxin (vasodilation)
Staphylococcus aureus; Toxic shock syndrome toxin TSST1 (hypotension, superantigen)
Bordetella pertussis; pertussis toxin (ADP-ribosylation of G proteins)
Corynebacterium diphtheriae; Diphtheria toxin (protein synthesis inhibitor)
Endotoxin: LPS in cell wall of Gram (-)

17. Capsule
Network of polymers (polysaccharide or protein) covering bacterial surface - S.pyogenes capsule: hyaluronic acid - S.pneumonia capsule: polysaccharide
Prevent C3 convertase formation by failing to bind serum protein B (no complement activation)
Antibody formation to capsule can be protective (vaccine)

18. Pathogenicity Islands
Different G+C content from host genome
Mobile genes associated with tRNA and/or insertion sequence (IS) elements
Carry multiple virulence factors
Large size

19. Host Evasion: Adherence sIgA Protease Iron Acquisition mechanisms
Intracellular residence: - vacuole - free in cytoplasm
Survive phagocytosis
Capsule; prevents phagocytosis
Evade antibody response: - Antigenic variation (pili, LPS, capsule) - Capsule that mimics host antigens
Prevent migration of phagocytes

20. Prevention
Vaccine to interfere with critical mechanism of host evasion - adherence mechanism - toxin
Antibacterial agents
Probiotics/Prebiotics

21. Overview Host Defenses Microbial Virulence Factors
Host Evasion Tactics