Transcript Host Defences, Microbial Evasion & Virulence Factors

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)
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
B
lymphocyte
Helper T
lymphocyte
(CD4)
Cytolytic T
lymphocyte
(CTL) (CD8)
Natural Killer
cell (NK)
Effector functions
Antibody
Secretion
Activation of
B & T cells
Macrophage
activation
Inflammation
Target cell
lysis
Target cell
lysis
Bacteria vs Antibacterial Agents MascarettiOA (ed) 2003
Superantigens
- S.pyogenes
- S.aureus
Pathogen
Disease
Host cell
Interaction
Skin/Tissue
Pneumonia
Whooping cough
Gonorrhea
UTI, diarrheas, meningitis
Ulcers, gastritis
Adherence
Adherence
Adherence
Adherence
Adherence
Adherence
Legionaires’ disease
Tuberculosis
Within vacuole
Within vacuole
Typhoid fever, gastroenteritis
Dysentery, gastroenteritis
Listeriosis, meningitis
Trachoma, STD, pneumonia
Within vacuole
Intracytoplasmic
Intracytoplasmic
Within vacuole
Extracellular:
-
S.aureus
-
S.pneumoniae
B. pertussis
N. gonorrhoeae
E.coli
H.pylori
-
to ECM
to ECM
to cells
to cells
to cells
to cells
Intracellular
Macrophages:
-
L. pneumoniae
M. tuberculosis
Macrophage &
Epithelial cells
-
Salmonella species
Shigella species
L.monocytogenes
Chlamydia species
Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Pili or adhesins
Prokaryotic Cell
Intracellular
Control of virulence factors:
(Pilin, capsule, invasins, toxins etc)
Receptor
Adherence blockers
Virulent Bacteria
Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Pili or adhesins
Prokaryotic Cell
Intracellular
Control of virulence factors:
(Pilin, capsule, invasins, toxins etc)
Receptor
COLONIZATION
Adherence blockers
Virulent Bacteria
Prokaryotic and Eukaryotic Interactions
Eukaryotic Cell
Prokaryotic Cell
Pili or adhesins
Intracellular
Control of virulence factors:
(Pilin, capsule, invasins, toxins etc)
Receptor
COLONIZATION
Virulent Bacteria
Adherence blockers
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)
Chaperone-Usher Pathway
Adhesin:
binds Gal(α1-4)Gal
A
A
Tip Fibrillum
A
A
Pilus Shaft
A
Usher
C
H
Gm(-) Bacterial
Periplasm
A
Cytoplasmic
membrane
A
H
A
A
D
Chaperone
I
B
Regulation
A
Pilus tip Fibrillum subunits
Pilus assembly machinery
Pilus
subunit
H
C
D
Anchor
Usher
Chaperone
J
K
E
F
G
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