Oxalyl-CoA decarboxylase is a major and specific virulence factor for Adherent Invasive Escherichia coli

Oxalyl-CoA decarboxylase is a major and specific virulence factor for Adherent Invasive Escherichia coli | 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 Oxalyl-CoA decarboxylase is a major and specific virulence factor for Adherent Invasive Escherichia coli David Skurnik, Eya Toumi, giovanna Orianne, Eric FRAPY, Loic Chollet, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8320012/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Adherent-invasive Escherichia coli (AIEC) are enriched in the gut microbiota of patients with Crohn’s disease (CD), but bacterial genes underlying their role in intestinal inflammation remain poorly defined. By integrating in vivo whole-genome transposon sequencing (TnSeq) with and without colitis conditions, RNA sequencing and mechanistic experiments, we identified oxc, which encodes oxalyl-CoA decarboxylase, as a major and specific determinant of AIEC virulence under inflammatory conditions. Disruption of oxc in AIEC, but not in laboratory or commensal E. coli strains, eliminated survival under acid and oxidative stress, reduced motility and biofilm formation, and suppressed adhesion, invasion, and intramacrophage persistence. In vivo, oxc was (i) required for AIEC survival in all gastrointestinal segments in colitis settings and (ii) exacerbated colitis severity. Transcriptomics analysis revealed repression of flagella and acid resistance systems encoding genes, linking metabolism to motility and stress defenses. Metabolically, loss of oxc suppressed prpBCDE operon induction at low pH and altered threonine/propionate and oxalate pathways, with concordant changes in energy and respiratory activities. Diet enriched in oxalate or propionate potentiated AIEC colonization and pathology in an oxc-dependent manner. Overall, oxc is linking metabolic to virulence pathways under inflammatory conditions and may represent a treatable target for microbiome-preserving interventions Biological sciences/Microbiology/Bacteria/Bacterial host response Health sciences/Pathogenesis/Inflammation/Chronic inflammation Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8320012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":572174638,"identity":"41e8dbe0-2de2-451f-bb5a-651455a21fca","order_by":0,"name":"David 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By integrating in vivo whole-genome transposon sequencing (TnSeq) with and without colitis conditions, RNA sequencing and mechanistic experiments, we identified oxc, which encodes oxalyl-CoA decarboxylase, as a major and specific determinant of AIEC virulence under inflammatory conditions. Disruption of oxc in AIEC, but not in laboratory or commensal E. coli strains, eliminated survival under acid and oxidative stress, reduced motility and biofilm formation, and suppressed adhesion, invasion, and intramacrophage persistence. In vivo, oxc was (i) required for AIEC survival in all gastrointestinal segments in colitis settings and (ii) exacerbated colitis severity. Transcriptomics analysis revealed repression of flagella and acid resistance systems encoding genes, linking metabolism to motility and stress defenses. Metabolically, loss of oxc suppressed prpBCDE operon induction at low pH and altered threonine/propionate and oxalate pathways, with concordant changes in energy and respiratory activities. Diet enriched in oxalate or propionate potentiated AIEC colonization and pathology in an oxc-dependent manner. \r\nOverall, oxc is linking metabolic to virulence pathways under inflammatory conditions and may represent a treatable target for microbiome-preserving interventions","manuscriptTitle":"Oxalyl-CoA decarboxylase is a major and specific virulence factor for Adherent Invasive Escherichia coli","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 02:48:24","doi":"10.21203/rs.3.rs-8320012/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b8cac1af-b826-4490-b8c4-cae42fe94d62","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60891333,"name":"Biological sciences/Microbiology/Bacteria/Bacterial host response"},{"id":60891334,"name":"Health sciences/Pathogenesis/Inflammation/Chronic inflammation"}],"tags":[],"updatedAt":"2026-02-23T12:50:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 02:48:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8320012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8320012","identity":"rs-8320012","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}