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25 Cards in this Set
- Front
- Back
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Virulence factors |
1. flagella 2. adherence factors 3. invasion factors 4. capsules 5. siderophores 6. endotoxins (LPS) 7. exotoxins 8. Secretion systems |
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Goal of virulence factors |
1. colonize host 2. invade host 3. cause disease 4. evade host defenses |
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Adherence of bacteria to epithelial cells. |
1.Essential first step for colonization and invasion process: requires adhesins on bacterial surface and receptors on host cell 2. Adhesion prevents physical removal of bacteria -fluids (saliva/urine) -peristalsis(gut) -sneezing(respiratory tract) 3. specific adhesion is associated with host and tissue tropism 4. many adhesins are also invasion factors (Invasins) -trigger signaling event for bacterial uptake. |
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Kinds of adhesins |
1. Pili or Fimbriae -hair-like fibers consisting of multiple subunits 2. Non-fimbrial adhesins -one protein |
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Adhesins |
1. Non-fimbrial adhesin -bald bacterial surface, adhesins embedded in surface 2. Fimbriae -Very hairy surface, thin filaments protruding from surface 3. Type IV pili -Rope-like structures made of many "threads" intertwined 4. Curli -Coiled surface structure intertwined. not rope-like; curved/curled |
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Uropathogenic E. coli |
1. UPEC responsible for majority of urinary tract infections (UTIs) -Cystitis (infection of bladder) -Pyelonephritis (infection of kidney) -Urosepsis (UTI spreads into bloodstream 2. UPEC attach and invade bladder epithelial cells |
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Intracellular bacterial communities |
1. UPEC Intracellular bacteria community protected from host immune system and drugs 2. responsible for recurrent infections |
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UPEC pili |
1. Type-1 pili are produced by 80% of UPEC 2. 200-5000 fimbriae 3. single type-1 fimbria is made up of 1000 copies of FimA major subunit |
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UPEC adhesins |
1. Type-1 pili: bind to mannose of glycoproteins 2. Pyelonephritis-associated (P) pili (pap genes) - bind to Galalpha1-->4Galbeta disaccharide present on glycosphingolipids of the kidney epithelium 3. S pili: bind sialic acid residues 4. Dr adhesins: bind Dr blood group Ag. |
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Genetic organization of pilus |
pilus genes organized in operons 1. Type 1 (9) - Regulators, major pilus subunit, periplasmic chaperone, OM usher, adaptors/initiator/terminator, Mannose bindign protein 2. P pilus (11) - Regulators, major pilus subunit, pilus anchor, OM usher, peiplasmic chaperone, adaptor/initiator |
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Components of pili |
Type-1 pilus: -Tip fibrillum components :FimH/G/F -major subunit: FimA
Pap pilus: -Tip fibrillum components: PapG/F/E/K -major subunit: PapA |
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Assembly of type-1 and Pap pili |
1. secretion of all subunits in periplasmic space 2. perisplamic chaperone (PapD) interacts with PapA/G/F/K preventing premature oligomerization. 3. PapD delivers them to OM usher(PapC) 4. Assembly is regulated in this order (GFEKA) |
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Structure of FimG usher |
1. there are 2 ushers, one is used for translocation 2. Arm complex extending from the unutilized usher bring the filaments to the outside |
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Donor-Strand exchange |
1. In periplasm, subunits are stabilized (they tend to aggregate)by chaperone that donates a beta strand to complement the subunits truncated immunoglobulin fold. 2. Assembly proceed with the complementary strand replaced by N-terminal extension of incoming pilus subunit. |
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Pap binding target |
1. PapG's side binds to globoside(GbO4) 2. Globoside (GbO4) is a glycosphingolipid that consists of tetrasaccharide GalNac --> GalAlpha1 --> 4GalBeta --> Glc linked to ceramide |
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Type-1 pili binding target |
1. FimH is sufficent to mediate uptake by bladder epithelial cell 2. function as adhesin and invasin. Trigger bacterial uptake upon binding |
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Type IV pili |
1. adhesion and auto-aggregation 2. Surface motility (twitching) 3. Microcolony and biofilm formation 4. phage attachment 5. DNA uptake by natural transformation |
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Twitching motility |
Type IV pili 2 steps process 1. Pili extend from the front of th cell 2. contact with the surface induces retraction, causes motility |
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Secretion pathways |
various types of pili are assembled through different dedicated secretion pathway 1. Chaperone-usher pathway (E.coli type-1 pili) |
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Therapeutic interventions against adhesin |
1.Competitive inhibition of adhesion: oral administration of biphenyl mannoside prophylatically 2. Inhibition of pilus assembly by 2-pyridone pillicides(bind to chaperone FimG, preventing it to interact with FimD outermembrane usher) |
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Non-fimbrial adhesins |
1. Invasin from Yersinia -Y. pseudotuberculosis -Y. enterocolitica 2. Bacteria are translocated across M cells into Payer's patches of small intestine 3. Interaction between Invasin and beta1-integrin receptors promotes bacterial internalization. |
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Invasin |
1. 986 residues protein, elongated, 18nm rod 2. N terminal consists of beta-barrel spanning OM 3. C-terminal (Extracellular) -Ig-like domains -D4 and D5 bind beta1-integrins |
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Invasin assembly |
Yersinia invasin is an autotransporter 1. forms beta-barrel in the OM, passenger domain translocates throug 2. Passenger domain can be cleaved or remain attached 3. LysM domain interacts with peptidoglycan(anchor) |
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beta1 integrins |
1. heterodimer (alpha/beta integral membrane protein) 2. normally, beta1 integrins bind ECM proteins (fibronectin(RGD motif). 3. target of yersinia invasin(higher affinity binding than fibronectin) 4. binding induces signaling leading to Yersinia invasion.
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Invasin induced signaling |
1.FAK autophosphorylation 2.SRC recruited via FAK -leads to RAC1 activation 3. RAC1 might activate WAVE 4. leads to actin recruitment(WAVE binds Arp2/3) resulting in bacterial engulfment. |
