University of Dundee

'How intestinal antibodies work'

Event Date: 
Wednesday, January 30, 2019 - 13:00 to 14:00
Event Location: 
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Dr. Mahima Swamy
Event Speaker: 
Prof Emma Slack
ETH Zurich
Event Type: 

All Welcome






How IgA mediates effector-less control of bacterial aggression and evolution in the intestinal lumen


High-avidity IgA protects from bacterial enteropathogens by directly neutralizing virulence factors, or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ("immune exclusion")1-3. Here we demonstrate, via mathematical modeling and Salmonella enterica serovar Typhimurium (S. Tm) vaccination and infection experiments, that IgA-mediated bacterial clumping is the major protective mechanism early in non-Typhoidal S. Tm infection. However, classical agglutination, which was thought to drive this process, requires pathogen cells to collide and is therefore only efficient at high (≥108 CFU/g) pathogen densities4,5. After ingestion of contaminated food, low densities (100-107 CFU/g 6) of rapidly dividing bacteria are present in the gut lumen. A distinctly different process clumps such growing bacteria: IgA enchains daughter cells, preventing their separation after division. This is expected to be a major protective process for all fast-growing IgA-targeted bacteria. As each clump is generated from a single clone, this has an additional effect beyond preventing tissue invasion and aiding clearance: Enchained growth also slows down bacterial evolution in vivo, for example by preventing exchange of conjugative plasmids between isolated clonal clumps. Enchained growth is therefore a mechanism by which multimeric antibodies can disarm and clear potentially invasive pathogens and pathobionts from the intestinal lumen without requiring inflammation or bacterial killing. Further, enchained growth can potentially be harnessed to combat the rise of antimicrobial resistance, which often spreads via conjugative plasmids7-10.