Show simple item record

dc.contributor.authorYu, Jason SL
dc.contributor.authorCorreia-Melo, Clara
dc.contributor.authorZorrilla, Francisco
dc.contributor.authorHerrera-Dominguez, Lucia
dc.contributor.authorWu, Mary Y
dc.contributor.authorHartl, Johannes
dc.contributor.authorCampbell, Kate
dc.contributor.authorBlasche, Sonja
dc.contributor.authorKreidl, Marco
dc.contributor.authorEgger, Anna-Sophia
dc.contributor.authorMessner, Christoph B
dc.contributor.authorDemichev, Vadim
dc.contributor.authorFreiwald, Anja
dc.contributor.authorMülleder, Michael
dc.contributor.authorHowell, Michael
dc.contributor.authorBerman, Judith
dc.contributor.authorPatil, Kiran R
dc.contributor.authorAlam, Mohammad Tauqeer
dc.contributor.authorRalser, Markus
dc.date.accessioned2022-04-23T01:01:55Z
dc.date.available2022-04-23T01:01:55Z
dc.date.issued2022-04
dc.identifier.issn2058-5276
dc.identifier.other35314781
dc.identifier.otherPMC8975748
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336390
dc.description.abstractMicrobial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways. Through analysis of auxotrophs for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial communities obtained as part of the Earth Microbiome Project (EMP), and study of auxotrophic-prototrophic interactions in self-establishing metabolically cooperating yeast communities (SeMeCos), we reveal a metabolically imprinted mechanism that links the presence of auxotrophs to an increase in metabolic interactions and gains in antimicrobial drug tolerance. As a consequence of the metabolic adaptations necessary to uptake specific metabolites, auxotrophs obtain altered metabolic flux distributions, export more metabolites and, in this way, enrich community environments in metabolites. Moreover, increased efflux activities reduce intracellular drug concentrations, allowing cells to grow in the presence of drug levels above minimal inhibitory concentrations. For example, we show that the antifungal action of azoles is greatly diminished in yeast cells that uptake metabolites from a metabolically enriched environment. Our results hence provide a mechanism that explains why cells are more robust to drug exposure when they interact metabolically.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101674869
dc.sourceessn: 2058-5276
dc.subjectDrug Tolerance
dc.subjectMetabolic Networks and Pathways
dc.subjectMetabolome
dc.subjectMicrobial Interactions
dc.subjectMicrobiota
dc.titleMicrobial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.
dc.typeArticle
dc.date.updated2022-04-23T01:01:53Z
prism.endingPage555
prism.issueIdentifier4
prism.publicationNameNat Microbiol
prism.startingPage542
prism.volume7
dc.identifier.doi10.17863/CAM.83807
dcterms.dateAccepted2022-01-28
rioxxterms.versionofrecord10.1038/s41564-022-01072-5
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidYu, Jason SL [0000-0001-5203-3603]
dc.contributor.orcidCorreia-Melo, Clara [0000-0001-6062-1472]
dc.contributor.orcidHerrera-Dominguez, Lucia [0000-0001-8276-2241]
dc.contributor.orcidWu, Mary Y [0000-0002-2074-6171]
dc.contributor.orcidHartl, Johannes [0000-0001-8470-5355]
dc.contributor.orcidEgger, Anna-Sophia [0000-0002-5204-7121]
dc.contributor.orcidHowell, Michael [0000-0003-0912-0079]
dc.contributor.orcidBerman, Judith [0000-0002-8577-0084]
dc.contributor.orcidAlam, Mohammad Tauqeer [0000-0002-6872-0691]
dc.contributor.orcidRalser, Markus [0000-0001-9535-7413]
dc.identifier.eissn2058-5276
pubs.funder-project-idEuropean Research Council (951475)
pubs.funder-project-idMedical Research Council (MC_UU_00025/11)
pubs.funder-project-idWellcome Trust (IA 200829/Z/16/Z, 200829/Z/16/Z, FC001134)
pubs.funder-project-idIsrael Science Foundation (ISF) (#997/18)
pubs.funder-project-idVersus Arthritis (FC001134)
pubs.funder-project-idFrancis Crick Institute (Francis Crick Institute Limited) (FC001134FC001134)
cam.issuedOnline2022-03-21


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International