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SUMMARY:IgA-mediated enchained growth mediates protection and modulates ba
 cterial evolution in the intestinal lumen - Dr Emma Slack\, Institute of M
 icrobiology\, ETH Zurich
DTSTART:20170322T160000Z
DTEND:20170322T170000Z
UID:TALK69322@talks.cam.ac.uk
CONTACT:Fiona Roby
DESCRIPTION:Secretory IgA is the only adaptive immune component present in
  the healthy intestinal lumen. This antibody isotope is dimeric but lacks 
 any known bactericidal effector function. How can this efficiently protect
  us from enteropathogens and dysbiosis? Combining detailed experimental an
 alysis in an oral vaccination / non-Typhoidal Salmonellosis model\, with a
  variety of computational analyses\, revealed a major gap in our understan
 ding of IgA biology. Bacterial clumping\, rather than virulence neutralisa
 tion accounted for the majority of high-avidity IgA-mediated protection. H
 owever\, classical agglutination\, generating clumped bacteria\, is only e
 fficient at high pathogen densities (≥1e8 CFU/g)\, rarely observed in re
 al infections. In fact\, a different physical process drives clump-formati
 on in vivo: IgA-mediated cross-linking enchains daughter cells\, preventin
 g their separation after division\, i.e. clumping is dependent on growth. 
 As this mechanism generates clonal clumps in the gut lumen\, it not only p
 rotects the host tissues\, but also has major implications for evolvabilit
 y of the targeted bacteria. For example IgA enchains plasmid-donor and -re
 cipient clones into separate clumps\, impeding conjugative plasmid transfe
 r in vivo.\n\nEnchained growth is therefore a mechanism by which IgA can d
 isarm and clear potentially invasive species from the intestinal lumen wit
 hout requiring high pathogen densities\, inflammation or bacterial killing
 . Furthermore\, it reveals an untapped potential for oral vaccines in comb
 atting the spread of antimicrobial resistance\n
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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