Comparative genomics reveals plasmid-encoded genes associated with Klebsiella infection in colonized patients

Comparative genomics reveals plasmid-encoded genes associated with Klebsiella infection in colonized patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparative genomics reveals plasmid-encoded genes associated with Klebsiella infection in colonized patients Jay Vornhagen, Emily Roberts, Lavinia Unverdorben, Sophia Mason, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1254643/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Aug, 2022 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Klebsiella frequently colonizes the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases (N = 85), where colonizing and invasive Klebsiella isolates were identical strain types, were matched to asymptomatically colonizing controls (N = 160). Thirty-seven genes were significantly associated with infection, 27 of which remained significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes were not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many infection-associated genes were plasmid borne, and for some, the relationship with infection was mediated by gut dominance. Five infection-associated genes were validated in a geographically independent cohort of colonized patients. This study identifies novel genes that are reproducibly associated with progression to infection in patients colonized by diverse Klebsiella. Full Text Additional Declarations Yes there is potential Competing Interest. KR is supported in part from an investigator-initiated grant from Merck & Co, Inc. and has consulted for Bio-K+ International, Inc., Roche Molecular Systems, Inc., and Seres Therapeutics. All other authors declare that they have no competing interests. Supplementary Files NatCommsSupplementaryInformation.docx SupplementaryTable1.xlsx SupplementaryTable2.xlsx SupplementaryTable3.xlsx SupplementaryTable4.xlsx SupplementaryTable5.xlsx SupplementaryTable6.xlsx SupplementaryTable7.xlsx SupplementaryTable8.xlsx SupplementaryTable9.xlsx 00694rsflat.pdf Reporting Summary Cite Share Download PDF Status: Published Journal Publication published 01 Aug, 2022 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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All other authors declare that they have no competing interests.","formattedTitle":"Comparative genomics reveals plasmid-encoded genes associated with Klebsiella infection in colonized patients","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-1254643/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-1254643/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1254643/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Klebsiella frequently colonizes the gut and colonization is associated with subsequent infection. 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