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Host Defenses, Microbial Evasion & Virulence Factors.

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Presentation on theme: "Host Defenses, Microbial Evasion & Virulence Factors."— Presentation transcript:

1 Host Defenses, Microbial Evasion & Virulence Factors

2 Overview Host Defenses Host Defenses Microbial Virulence Factors Microbial Virulence Factors Host Evasion Tactics 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 Microbial Pathogenesis and the Intestinal Epithelial Cell 2003 Hecht GA (Editor) Pattern recognition receptors (PRR); produce lymphokines when stimulated

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

6 Superantigens - S.pyogenes - S.aureus

7 PathogenDisease Host cell Interaction Extracellular: - S.aureus - S.pneumoniae - B. pertussis - N. gonorrhoeae - E.coli - H.pylori Skin/TissuePneumonia 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 IntracytoplasmicIntracytoplasmic

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

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

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

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 AHCDJKEFG Pilus assembly machinery UsherChaperone Pilus tip Fibrillum subunits BI Anchor Gm(-) Bacterial Periplasm H A D A A H A A A A A A C C Pilus subunit Adhesin: binds Gal (α1-4) Gal Pilus Shaft Usher Tip Fibrillum Chaperone Chaperone-Usher Pathway Regulation Cytoplasmic membrane

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

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

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

21 Overview Host Defenses Host Defenses Microbial Virulence Factors Microbial Virulence Factors Host Evasion Tactics Host Evasion Tactics


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