{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:10:47Z","timestamp":1788891047899,"version":"build-2803163510"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"954","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI164687"],"award-info":[{"award-number":["R01 AI164687"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI174999"],"award-info":[{"award-number":["U19 AI174999"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK007673-30"],"award-info":[{"award-number":["T32 DK007673-30"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    The Gram-positive opportunistic pathogen\n                    <jats:italic toggle=\"yes\">Clostridioides difficile<\/jats:italic>\n                    colonizes the gut by adapting to an array of threats from the host and the microbiome. A potential threat from the microbiome is the antimicrobial peptide bacitracin, which is produced by the commensal\n                    <jats:italic toggle=\"yes\">Bacillus licheniformis<\/jats:italic>\n                    and prevents dephosphorylation and recycling of undecaprenyl phosphate, a lipid carrier essential in cell wall biogenesis. Gram-positive bacteria typically use multiprotein membrane complexes called Bce modules to sense and respond to bacitracin. We identified a Bce module in\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    that incorporates the undecaprenyl pyrophosphatase BacA2 into the bacterium\u2019s response to bacitracin. This Bce module was essential for\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    survival in the presence of\n                    <jats:italic toggle=\"yes\">B. licheniformis<\/jats:italic>\n                    or bacitracin in vitro and in mice. Expression of the genes encoding the Bce module was inhibited by Fur, a transcriptional repressor that controls the expression of genes critical for responding to host-mediated restriction of iron availability in the gut. Low iron reduced undecaprenyl phosphate biosynthesis and sensitized\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    to bacitracin. Our findings support a model in which\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    is affected independently and collectively by low iron and bacitracin, leading to the inhibition of undecaprenyl phosphate recycling. In response,\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    increases the transcription of undecaprenyl recycling and bacitracin efflux genes that are controlled both by Fur and a Bce module. This distinct Bce module forms a system that responds to nutritional immunity and antimicrobial molecules produced by microbiome members to maintain envelope integrity and support host colonization.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.aef8846","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:58:25Z","timestamp":1788890305000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["<i>Clostridioides difficile<\/i>\n                    couples responses to host nutritional immunity and a commensal-derived antibiotic to enable growth in the gut"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-557X","authenticated-orcid":true,"given":"Martin V.","family":"Douglass","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren R.","family":"Melton","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-4699","authenticated-orcid":true,"given":"M. Wade","family":"Calcutt","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4274-6022","authenticated-orcid":true,"given":"Tess P.","family":"McNeely","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4392-7506","authenticated-orcid":true,"given":"Sarah L.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew 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