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44 Cards in this Set

  • Front
  • Back
How are flagella involved in pathogenesis?
Motility
Adhesion to and invasion of host cells
Flagella and biofilms
Flagellar phase variation
Mucosal inflammatory response to flagellin
How are bacterial motile?
Can use their flagella to swim
How many genes are required for the flagellar machinery to be expressed?
about 50
How are bacteria motile?
They attach with their flagella
What are examples of motile bateria?
Non motile?
Motile: E. coli (many flagella), Pseudomonas aeruginosa (single flagellum)
Non motile: S. aureus
Do bacteria have flagella when they're in a biofilm?
No, don't swim in biofilm, .: don't need flagella
->When biofilm disperses, bacteria produce the genes for flagella
Why is flagellin important in producing inflammation?
1) TLR5 -> extracelllular receptor
2) Intracellular receptor
Both these work together to produce inflammation
What are the 2 flagellin genes important for motility?
FliC
FljB
What happens to mutants that don't have FliC or Fljb?
No motility
Why is the expression of flagellar motility genes tightly regulated?
Assure ordered ptn assembly
How are the flagellar machinery genes transcribed?
First: early genes
then intermediate genes
then late genes
What do the early genes code for?
Rings (get channel formation)
What are the late genes for?
Hook and filament ptns
-> go through channels to outside to form the flagella
Where are the early transmb ptn transported through?
Sec-pathway
->go from cytoplasm (where synthesized) to periplasm (where assembled)
How are the later ptns transported outside ?
The Flagellar-specific export path
How many flagellin subunits does the filament have?
30,000
Where does the E for flagellin rotation come from?
Mb gradient of H+
Where do H+ move through?
8 independent force-generating units (Mot ptns)
-> These form the Stator (stationary part of the motor)
What do the H+ interact with?
ring of ~32 FliG ptns that form the Rotor
(drives the rotation)
How many rotations/sec?
H+/rotation?
Speed?
250 rotations/sec
1000 H+/rotation
Speed: 15-100um/sec
How many flagella does P. aeruginosa have?
1 polar flagellum
What is FliC?
Flagellin
What is FliD?
Flagellar cap ptn
What does P.aeruginosa do in cystic fibrosis patients?
Colonizes the airway lumen
What does FliD bind to?
Mucin (MUC-1), a cell surface-associated mucin
How is a biofilm produced?
Unattached cells --> Attach to the surface => Surface growth
->get attached monolayer (where they move with appendages other than flagella)
=>bacteria produce Type IV pili (glide along surface by extending and retracting the pili)
->Form a microcolony
->use quorum sensing to sense their env't
Once in a biofilm, they no longer swim, .: they usually don't express flagella
What is a biofilm?
Bacteria embedded in a matrix consisting mostly of secreted polysac
What happens in flagellar phase variation of Salmonella?
Depending on which phase flagella dev'p is in, different Fli genes will be expressed
What are the 2 genes coding for flagellin?
FljB and FliC
(Don't need both, onl one or the other)
What is FljA?
What does it do?
Transcriptional repressor
Lines up with promoter of FliC and represses, so only 1 gene (Flj B) is transcribed
What is the 996 bp segment of Salmonella?
promoter for fljB and fljA
What happens from this gene is inverted?
Orientation of the promoter dif, .: dont make Flj A/B .: no fjA to repress T of FliC
-> Transcribe FliC

->if Flj T, FljA blocks FliC
-> If promoter of Flj inverted, no FljA, .: get FliC
What is the purpose of flagellar phase variation?
Ab made vs FljB wont recognize FliC
.: Bacteria can evade host for longer
What does Hin recombinase do?
Catalyzes the inversion of the Flj promoter
What does TLR5 do?
senses flagellin monomers
What happens during signalling through TLR5?
Activation of NF-kB and MAPK paths that turn on T of genes involved in innate and adaptive immunity
Do the flagellin monomers from Heliobacter pylori cause inflammation?
No
Why are there different lvls of inflammation produced by flagellin?
Dif bacteria use different genes to transcribe the flagellin
.: different response
What kind of a response is triggered by Salmonella flagellin monomers?
Robust inflammatory response (IL-8 and other chemokines)
This attracts PMNs
What do TLRs recognize?
PAMPs (pathogen associated molecular patterns)
What is Ipaf?
Cytoplasmic receptor of flagellin
Part of NOD-like receptors
What happens when flagellin interacts with Lpaf?
Activates Caspase-1
What happens when TLR5 interats with flagellin?
Interacts with MyD88, which gets rid of IkB and allows NF-kB to translocate into the nucleus and trigger innate I.S and start the adaptive response
LIST of TLRs on pg 11
LIST of TLRs on pg 11