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High-avidity IgA protects the intestine by enchaining growing bacteria
ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.;Univ Zurich, Ctr Dent Med, Zurich, Switzerland..
ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
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2017 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 544, no 7651, 498-+ p.Article in journal (Refereed) Published
Abstract [en]

Vaccine-induced high-avidity IgA can protect against 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). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, 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, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 544, no 7651, 498-+ p.
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-322172DOI: 10.1038/nature22058ISI: 000400051900047PubMedID: 28405025OAI: oai:DiVA.org:uu-322172DiVA: diva2:1096154
Funder
German Research Foundation (DFG), VO 2273/1-1Swedish Research Council, 2012-262 2015-00635
Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2017-05-17Bibliographically approved

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