Lecture 19 - Adhesins Flashcards
(21 cards)
define colonisation and list the 2 primary sites
- Colonisation = establishment of stable bacterial population in host; critical 1st step
1. skin/epidermis
2. mucosal epithelia
what are the 2 colonisation outcomes? give bacterial examples
- pathogen confined to eptihelial surface eg V cholerae, Bordetella pertussis
- pathogen crosses epithelia and invades eg S enterica typhi, legionella
what are the 2 barriers to colonisation in the mucosal epithelia?
- mucous from goblet cells and subepithelial glands
- mucins = filamentous glycosylated proteins tha bind and trap pathogens by receptors
how does attachment relate to colonisation? what can prevent it?
- attach = overcome mechanical removal to allow colonisation
- mechanical removal = blinking, chewing, fluid flow etc
what are the 3 requirements of colonisation?
- not trapped in mucous
- penetrate mucous to reach epithelia = flagella or mucinases
- adhesion to epithelia
define adhesins and the 2 types
- specialised surface structures that bind specific host receptors
1. fimbrial/pilus = protruding pili with adhesin @ tip
2. afimbrial = no structure (?); tight binding after depolymerisation of fimbrial/pilus adhesion (in G-ve?)
what is the purpose of the fimbrial/pilus type adhesins?
host and bacteria -ve charged = repulsion so pilus extending past capusle + gap between allows binding
describe the general features of pili and fimbriae
- hair-like protein organelles
- 5-7nm wide, 0.5-10+ mm long, peritrichous/polar, varied morphology, few-hundreds per cell
describe the 2 structural components of a pilus
- shaft/rod = pilin subunits in helical array
- adhesive subunit/s = specialised Tip protein structure @ end/along rod
list the 6 proteins in the structure of the pyelonephritis associated pili (Pap) in EPEC
- PapC, D and H in OM
- PapA (x1000) forming rod
- PapK joining rod and fibril
- PapE (x5-10) forming fibril
- PapF joining fibril and adhesin
- PapG adhesin
describe the structure of fibrillae and 1 bacterial example
- finer fibrous organelles 2-3nm wide
- multidomain proteins = adhesive domain and tandem repeat domains = stalk
eg s aureus’ M protein = collagen/fibronectin binding subunits
what is the reason for the receptor specificity of pili? give 2 bacterial examples
- determines tissue colonised
- eg1 specific pap pili of UPEC = PapG to globotriasylceramide receptor
- eg2 non-specific type 1 pilus of UPEC = FimH to mannose glycoprotein receptor bc mannose in most cells eg bladder
list the adhesins and their receptor for ETEC, EPEC and UPEC
- ETEC = K88 pilus for pigs, K99 pilus for cow/sheep/pig, CFA1/2 for humans
- EPEC = bfp for human urinary tract
- UPEC = Pap and type 1 pili for human urinary tract
explain how anti-virulence antimicrobials work
- inhibit virulence not growth = resistance not a survival advantage so no theoretically no resistance
- potential specis/strain specific = doesn’t harm microbiome
Discuss adhesins as vaccine candidates and how it works + difficulties
- block binding + opsonise pathogen
- K88 pilus vaccine for pig ETEC
- K99 pilus vaccine for calves/pigs/lamb ETEC
- FimH pilus vaccine for human EPEC
- difficult bc 25+ pilus types = target main ones
explain how the anti-adhesin stable high affinity receptor analogue drug works with 2 disease examples
- competitively inhibit adhesin to prevent colonisation
- eg UPEC = gal-alpha-1,4-gal analogues to bind PapG + mannoside analogues to bind type 1 pilus
- eg2 Crohn’s disease = mannoside analogue to block FimH adhesin
explain how the anti-adheisn inhibitor of pilus assembly drug works
- conserved chaperones bind C-terminal Pap and type 1 pilus subunits
- target chaperons with 2-pyridones = PapG analogues
- decreased UPEC binding bladder by 90%
what are 4 problems identified with anti-adhesin drugs?
- cocktail of vaccines bc multiple adhesins
- rapid precise pathogen diagnosis
- non-specific drugs interferes with microbiome
- weak activity in vivo (but still decreased binding)
how do commensal bacteria promote colonisation resistance/
- indirect = microbiota stimulated host immunity
- direct = competition for nutrients/niche + make antimicrobials
what are bacteriocins and give 1 example
- Small antibacterial proteins from normal flora
- eg Strep mutans inhibiting other strep eg s pyogenes causing pharyngitis
what are the 3 mechanisms of bacteriocins?
- community invasion = niche clearance of bacteriocin sensitive
- preventing invasion = invading sensitive cells killed
- community differentiation and spatial segregation = invading producer clears space
