{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:21:55Z","timestamp":1781108515944,"version":"3.54.1"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"17","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Societe Academique de Geneve","award":["SACAD"],"award-info":[{"award-number":["SACAD"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_219227"],"award-info":[{"award-number":["310030_219227"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"PMO | National Research Foundation Singapore","doi-asserted-by":"publisher","award":["SCELSE"],"award-info":[{"award-number":["SCELSE"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["2020-T1-002-103"],"award-info":[{"award-number":["2020-T1-002-103"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"MOH | National Medical Research Council","doi-asserted-by":"publisher","award":["MOH-000645"],"award-info":[{"award-number":["MOH-000645"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001474","name":"Singapore-MIT Alliance for Research and Technology Centre","doi-asserted-by":"publisher","award":["AMR IRG"],"award-info":[{"award-number":["AMR IRG"]}],"id":[{"id":"10.13039\/501100001474","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>\n                    Daptomycin is a last resort antibiotic used to treat vancomycin-resistant enterococcal infections, but daptomycin resistance (DAP\n                    <jats:sup>R<\/jats:sup>\n                    ) arises quickly during treatment. Resistance is due to sequential acquisition of point mutations in the two-component system LiaFSR and in cardiolipin synthases and is associated with alteration of phospholipid and glycolipid membrane composition. The molecular mechanisms underlying these lipid changes are currently unknown. Similarly, it is unclear why mutations in\n                    <jats:italic toggle=\"yes\">liaFSR<\/jats:italic>\n                    occur prior to mutations in\n                    <jats:italic toggle=\"yes\">cls<\/jats:italic>\n                    . We found that\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                    <\/jats:italic>\n                    remodels membrane composition as a phenotypic response to daptomycin that parallels the membrane composition of DAP\n                    <jats:sup>R<\/jats:sup>\n                    strains. The enrichment in glycolipids that follows antibiotic exposure is due to LtaS1, the main lipoteichoic acid (LTA) synthase of\n                    <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                    . LTA production is primarily governed by LiaFSR and SapRS, which directly couples antibiotic sensing with membrane lipid remodeling. Together, our results provide a unifying mechanism that drives phenotypic membrane fortification in a gram-positive pathogen which simultaneously predisposes the cell to acquire genetic high-level daptomycin resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2532437123","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:25:41Z","timestamp":1776788741000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-4977","authenticated-orcid":false,"given":"Cristina","family":"Colomer-Winter","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-4958","authenticated-orcid":false,"given":"Zeus J.","family":"Nair","sequence":"additional","affiliation":[{"name":"Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group","place":["Singapore, Singapore"]},{"name":"Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome Y. J.","family":"Chua","sequence":"additional","affiliation":[{"name":"Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1257-9977","authenticated-orcid":false,"given":"Soukayna","family":"Jabli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-8434","authenticated-orcid":false,"given":"M\u00e9lanie","family":"Roch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva","place":["Geneva, 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Colomer-Winter Data from \u201cA two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin.\u201d Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE309958. 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