A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin

Article Article scientifique Article A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin eng 2026-04-21 2026-04-28 author Colomer Winter Cristina 0000-0003-0103-4977 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland. 402413 Département de microbiologie et médecine moléculaire (MIMOL) author Nair Zeus J 0000-0001-9662-4958 Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Singapore 138602, Singapore.,Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore. author Chua Jerome Y J Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore. author Jabli Soukayna 0009-0004-1257-9977 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland. 963811 author Roch Mélanie 0000-0001-6485-8434 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland. 884710 Département de microbiologie et médecine moléculaire (MIMOL) author Cazenave-Gassiot Amaury 0000-0002-3050-634X Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.,Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore. author Sierra Roberto Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland.,Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School, Geneva 1211, Switzerland. 724681 Roberto Mario Sierra Miranda author Andrey Diego Olivier 0000-0003-3247-9274 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland.,Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School, Geneva 1211, Switzerland.,Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and University of Geneva, Geneva 1211, Switzerland. 542856 Département de médecine (DEMED) author Chng Shu-Sin 0000-0001-5466-7183 Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.,Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore 119077, Singapore. author Kline Kimberly Ann 0000-0002-5472-3074 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva 1211, Switzerland.,Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Singapore 138602, Singapore.,Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore. 984962 Département de microbiologie et médecine moléculaire (MIMOL) e2532437123 10.1073/pnas.2532437123 42012956 0027-8424 PMC13123819 https://pnas.org/doi/10.1073/pnas.2532437123 Daptomycin is a last resort antibiotic used to treat vancomycin-resistant enterococcal infections, but daptomycin resistance (DAPR ) 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 liaFSR occur prior to mutations in cls . We found that Enterococcus faecalis remodels membrane composition as a phenotypic response to daptomycin that parallels the membrane composition of DAPR strains. The enrichment in glycolipids that follows antibiotic exposure is due to LtaS1, the main lipoteichoic acid (LTA) synthase of E. faecalis . 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. Enterococcus faecalis LTA Daptomycin resistance Lipid remodeling Two-component systems Dewey 616 Societe Academique de Geneve SACAD PMO | National Research Foundation Singapore SCELSE Ministry of Education - Singapore 2020-T1-002-103 MOH | National Medical Research Council MOH-000645 Singapore-MIT Alliance for Research and Technology Centre AMR IRG Swiss National Science Foundation Phenotypic adaptation to hypoxia by Enterococcus faecalis during colonization and infection 219227 CH 54 Département de microbiologie et médecine moléculaire 21B 56 Département de médecine 221 false 1396 Pathogenesis of biofilm-associated infections 1044 1434 Infections bactériennes multi-résistantes 1060 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309958 Proceedings of the National Academy of Sciences of the United States of America 123 17 a902f633-1bf6-49d4-b55b-abcd11daf7d1 Article (Published version) Public 2026_Colomer_Winter_PNAS.pdf 3832834 application/pdf CC BY-4.0 1cb430fd310d1ccd09970e24b590b7104a45a7c380098012c92022850a6c39c2 fce202eb-fa3a-4375-8686-4492d47954ac Supplemental data Public pnas.2532437123.sapp.pdf 1138562 application/pdf a14349a442b0fe3aa4464f86bef339f73908c006521b375f93e1ae42e0c90890 4fcd957a-93b0-41de-b1bb-e2a8f681477b Supplemental data Public pnas.2532437123.sd01.xlsx 82021 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet f20b80050c1c6d8311bef22d844d416df0abe80db6642323e2b163b1daeea034 6e247853-fc5b-4099-995c-5a7b9ce029ef Supplemental data Public pnas.2532437123.sd02.xlsx 42133 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 9bea15f3572abe0a5ddb68f06d40b7e1dcb5cc96b4331e83cad0e3f069d8b810 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de médecine

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A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin	Proceedings of the National Academy of Sciences of the United States of America	2026	1	0
Characterization of Lipoteichoic Acid Synthases (LtaSs) in Enterococcus faecalis		2025	44	2

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