Regulation of virulence factors Flashcards
what is the structure of Fimbriae?
- Thread-like surface structures, 7 nm diameter,
- 5-2 μm long
- Repeating protein subunits, helical structure, central pore
- 500 fimbriae per cell, 1000 protein subunits
whats the role of fimbriae?
- Promote specific adhesion via protein adhesins
- Overcome electrostatic repulsion
- Promote adhesion to target carbohydrate receptors
give an example of phase variation in E. coli
- express different fimbriae with different specificities for host cell carbohydrate receptors
- bacterium will not express all fimbrial types at any given time
- ability to express different types of fimbriae allows bacteria to colonise different cell types as infection progresses
what are the characteristics of P-pili of uropathogenic E. coli
- 9 serotypes
- Cause haemagglutination P-group blood
- Ligand on bladder, ureter and renal tissue
- Mutants deficient in P-pili reduced virulence
- Maternal antibodies against P-pili are protective
Signalling Events Associated P-pili (Type I fimbriae) Mediated Adhesion
- Release ceramide TLR4 agonist
- Activate TLR4
- Release pro-inflammatory cytokines (Il-6 and CXCL8)
- Recruite neutrophils (clearance/damage)
- Tissue damage forms intracellular bacterial communities
- Persistent infection
Why regulate expression in pap?
- Large structure requiring multiple resources to synthesize
- Activates innate host immune responses
- Major target of adaptive immune responses
give an example of Stochastic Regulation
Genetic Variation (e.g. mutation)
give an example of Programmed Regulation
transcriptional regulons
describe the mechanisms evolved to respond to environmental signals in the pap operon
- expression regulated by temperature, catabolite repression (nutrient status)
- efficient expression of pap operon requires positive regulators PapB and PapI
- Phase variation depends on activity of Lrp
what is UAS?
Upstream Activator Sequence
whats the purpose of UAS?
contains promoters/binding sites for regulation by temperature, catabolite repression, transcriptional activators PapB/I, and by the global regulator Lrp
how does Temperature regulate pap?
26 C - H-NS binding represses transcription from PB - no fimbriae
37 C - Weak/no H-NS binding activates transcription of papB from PB – fimbriae produced
describe Catabolite repression at the pap operon
- Binding of cAMP with CRP is required for transcription of papB operon
- High levels of intracellular cAMP in poor growth conditions (e.g. in the urinary tract)
- ‘bends’ DNA, makes promoters accessible to RNA polymerase
explain pap gene Regulation by PapB
- Binding of PapB to sites in the UAS is required for efficient regulation of the papB operon
- Three PapB binding sites are occupied sequentially in response to increasing levels of PapB protein
describe the sites of PapB
• site 1: occupied when [PapB] (and [PapI]) low; PB
activated ⇒ increased PapB production.
• site 2: occupied as [PapB] increases, progressively preventing RNA polymerase binding ⇒ decreasedpapBoperonexpression.
• site 3: occupied if cellular [PapB] very high ⇒ switches off papB operon expression (autogenous regn.)
