Host Defenses, Microbial Evasion

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Host Defenses, Microbial Evasion Virulence
Factors
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• M. Alfa
• St Boniface General Hospital

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Overview

• Host Defenses
• Microbial Virulence Factors
• Host Evasion Tactics

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Host Defenses

Bacteria vs Antibacterial Agents 2003 Mascaretti
OA (editor)
No bacteria can penetrate intact skin
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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)
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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
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Superantigens - S.pyogenes - S.aureus
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(No Transcript)
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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
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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
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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
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Bacterial Invasion Conserved macromolecular
systems

• Adherence (attachment)
• Entry into body
• Avoidance of host immune defense
• Damage (tissue or functionality)
• Resist antibacterial agents

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Adhesion

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

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Chaperone-Usher Pathway
Adhesin binds Gal(a1-4)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
A
H
C
D
J
K
E
F
G
B
I
Usher
Chaperone
Anchor
Regulation
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Nonpilus Adhesin
Intimin (Enteropathogenic E.coli)
Microbial Pathogenesis and the Intestinal
Epithelial Cell 2003 Hecht GA (Editor)
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Toxins
Listeriolysin O
Superantigense.g. Spe, TSST1
Bacteria vs Antibacterial Agents 2003 Mascaretti
OA (editor)
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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 (-)
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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)

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Pathogenicity Islands

• Different GC content from host genome
• Mobile genes associated with tRNA and/or
  insertion sequence (IS) elements
• Carry multiple virulence factors
• Large size

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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

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Prevention

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

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Overview

• Host Defenses
• Microbial Virulence Factors
• Host Evasion Tactics