University of Cambridge > > Departmental Seminar Programme, Department of Veterinary Medicine > IgA-mediated enchained growth mediates protection and modulates bacterial evolution in the intestinal lumen

IgA-mediated enchained growth mediates protection and modulates bacterial evolution in the intestinal lumen

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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 analysis in an oral vaccination / non-Typhoidal Salmonellosis model, with a variety of computational analyses, revealed a major gap in our understanding of IgA biology. Bacterial clumping, rather than virulence neutralisation accounted for the majority of high-avidity IgA-mediated protection. However, classical agglutination, generating clumped bacteria, is only efficient at high pathogen densities (≥1e8 CFU /g), rarely observed in real infections. In fact, a different physical process drives clump-formation in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, i.e. clumping is dependent on growth. As this mechanism generates clonal clumps in the gut lumen, it not only protects the host tissues, but also has major implications for evolvability of the targeted bacteria. For example IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo.

Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, it reveals an untapped potential for oral vaccines in combatting the spread of antimicrobial resistance

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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