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Host Defenses, Microbial Evasion & Virulence Factors

Host Defenses, Microbial Evasion & Virulence Factors. Overview. Host Defenses Microbial Virulence Factors Host Evasion Tactics. Host Defenses. **. Bacteria vs Antibacterial Agents 2003 Mascaretti OA (editor). ** No bacteria can penetrate intact skin.

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Host Defenses, Microbial Evasion & Virulence Factors

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  1. Host Defenses, Microbial Evasion & Virulence Factors

  2. Overview • Host Defenses • Microbial Virulence Factors • Host Evasion Tactics

  3. Host Defenses ** 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. 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

  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 COLONIZATION

  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 INVASION COLONIZATION

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

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

  12. 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 Pilussubunit I B A H C D J K E F G Regulation Anchor Usher Chaperone

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

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

  15. 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 (-)

  16. 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)

  17. 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

  18. 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

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

  20. Overview • Host Defenses • Microbial Virulence Factors • Host Evasion Tactics

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