Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages

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dc.contributor.authorCortés-Martín, Adriánen
dc.contributor.authorButtimer, Colinen
dc.contributor.authorMaier, Jessie L.en
dc.contributor.authorTobin, Ciara A.en
dc.contributor.authorDraper, Lorraine A.en
dc.contributor.authorRoss, R. Paulen
dc.contributor.authorKleiner, Manuelen
dc.contributor.authorHill, Colinen
dc.contributor.authorShkoporov, Andrey N.en
dc.contributor.funderHorizon 2020en
dc.contributor.funderEuropean Research Councilen
dc.contributor.funderWellcome Trusten
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2025-07-07T10:45:50Z
dc.date.available2025-07-07T10:45:50Z
dc.date.issued2025-05-23en
dc.description.abstractBacteriophages (phages) and bacteria within the gut microbiome persist in long-term stablecoexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employa variety of mechanisms to evade phage infection, while phages rely on counterstrategies toovercome these defenses. Among the most abundant phages in the gut are the crAss-like phagesthat infect members of the order Bacteroidales, in particular, genus Bacteroides. In this study, weexplored some of the mechanisms enabling the co-existence of four phage-Bacteroidales hostpairs in vitro using a multi-omics approach (transcriptomics, proteomics and metabolomics). Theseincluded three Bacteroides species paired with three crAss-like phages (Bacteroides intestinalis andфcrAss001, Bacteroides xylanisolvens and фcrAss002, and an acapsular mutant of Bacteroidesthetaiotaomicron with DAC15), and Parabacteroides distasonis paired with the siphovirus фPDS1.We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechan-ism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternativeresistance mechanisms, while potentially less efficient than CPS phase variation, can be activatedto support bacterial survival by regulating gene expression and resulting in metabolic adaptations,particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phasevariation, enable bacterial populations to persist in the presence of phages, and vice versa. Anacapsular variant of B. thetaiotaomicron demonstrated broader transcriptomic, proteomic, andmetabolomic changes, supporting the involvement of additional resistance mechanisms beyondCPS variation. This study advances our understanding of long-term phage–host interaction, offer-ing insights into the long-term persistence of crAss-like phages and extending these observationsto other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions isessential for designing effective phage therapies and improving human health through targetedmicrobiome interventions.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid2507775en
dc.identifier.citationCortés-Martín, A., Buttimer, C., Maier, J. L., Tobin, C. A., Draper, L. A., Ross, R. P., Kleiner, M., Hill, C. and Shkoporov, A. N. (2025) ‘Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages’, Gut Microbes, 17(1), 2507775. https://doi.org/10.1080/19490976.2025.2507775en
dc.identifier.doi10.1080/19490976.2025.2507775en
dc.identifier.issued1en
dc.identifier.journaltitleGut Microbesen
dc.identifier.urihttps://hdl.handle.net/10468/17683
dc.identifier.volume17en
dc.language.isoenen
dc.publisherTaylor & Francisen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-COFUND-FP/101034270/EU/INnovative Sustainable Development InterdisciPlinary Post-Doctoral Research Excellence/INSPIREen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::ERC::ERC-COG/101001684/EU/PHAGENET: PHAge GEnetic NETworking in the microbiome/PHAGENETen
dc.relation.projectinfo:eu-repo/grantAgreement/WT/Pathogen Biology and Disease Transmission/220646//crAssphages - the most abundant viruses of the human gut/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Research Centres Programme::Phase 2/12/RC/2273_P2/IE/APC_Phase 2/en
dc.rights© 2025, the Authors. Published with license by Taylor & Francis Group, LLC.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the AcceptedManuscript in a repository by the author(s) or with their consent.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectBacteriophagesen
dc.subjectGut microbiomeen
dc.subjectIntestinal microbiotaen
dc.subjectPhage-bacteriainteractionen
dc.subjectViromeen
dc.subjectCrassphagesen
dc.subjectBacteroidesen
dc.subjectParabacteroidesen
dc.subjectCrassviralesen
dc.subjectCo-cultureen
dc.titleAdaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophagesen
dc.typeArticle (peer-reviewed)en
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