Host Defenses, Microbial Evasion & Virulence Factors

Overview Host Defenses Microbial Virulence Factors Host Evasion Tactics

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

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)

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

Superantigens - S.pyogenes - S.aureus

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

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

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

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

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

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

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

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

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

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 (-)

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)

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

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

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

Overview Host Defenses Microbial Virulence Factors Host Evasion Tactics