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dc.contributor.authorAguirre, Andrea Martinez
dc.contributor.authorYalcinkaya, Nazli
dc.contributor.authorWu, Qinglong
dc.contributor.authorSwennes, Alton
dc.contributor.authorTessier, Mary Elizabeth
dc.contributor.authorRoberts, Paul
dc.contributor.authorMiyajima, Fabio
dc.contributor.authorSavidge, Tor
dc.contributor.authorSorg, Joseph A
dc.date.accessioned2021-10-29T11:14:29Z
dc.date.available2021-10-29T11:14:29Z
dc.date.issued2021-10-19
dc.identifier.citationAguirre AM, Yalcinkaya N, Wu Q, Swennes A, Tessier ME, Roberts P, et al. (2021) Bile acid-independent protection against Clostridioides difficile infection. PLoS Pathogens, 17(10): e1010015. https://doi.org/10.1371/journal.ppat.1010015en
dc.identifier.issn1553-7366en
dc.identifier.doi10.1371/journal.ppat.1010015en
dc.identifier.urihttp://hdl.handle.net/2436/624427
dc.description© 2021 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.ppat.1010015en
dc.description.abstractClostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.en
dc.description.sponsorshipThis work was supported by R01AI116895 to J.A.S.; U01AI124290, R01AI100914, P01AI152999, R01NR013497 to T.S.; P30DK56338 to A.S. from the NIH (www.nih.gov) and a CONACYT-COECYT (https://coecytcoahuila.gob.mx/) fellowship 2017-2022 scholar/scholarship 625561/472087 to A.M.A.en
dc.formatapplication/pdfen
dc.languageeng
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urlhttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010015en
dc.subjectclostridioides difficileen
dc.subjectbile aciden
dc.subjectC. difficileen
dc.titleBile acid-independent protection against Clostridioides difficile infectionen
dc.typeJournal articleen
dc.identifier.eissn1553-7374
dc.identifier.journalPLoS Pathogensen
dc.date.updated2021-10-28T10:38:52Z
pubs.place-of-publicationUnited States
dc.date.accepted2021-10-07
rioxxterms.funderNIH and CONACYT-COECYTen
rioxxterms.identifier.projectR01AI116895en
rioxxterms.identifier.projectU01AI124290en
rioxxterms.identifier.projectR01AI100914, P01AI152999, R01NR013497en
rioxxterms.identifier.projectP30DK56338en
rioxxterms.identifier.project625561/472087en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2021-10-29en
dc.source.volume17
dc.source.issue10
dc.source.beginpagee1010015
dc.description.versionPublished online
refterms.dateFCD2021-10-29T11:13:08Z
refterms.versionFCDVoR
refterms.dateFOA2021-10-29T11:14:30Z


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