{"doi":"10.1016/j.jbc.2025.110276","title":"The VanS sensor histidine kinase from type-B vancomycin-resistant enterococci recognizes vancomycin directly","abstract":"Vancomycin-resistant enterococci (VRE) are high-priority targets for new therapeutic development. In VRE, expression of the resistance phenotype is controlled by the VanRS two-component system, which senses the presence of the antibiotic and responds by initiating transcription of resistance genes. VanS is a transmembrane sensor histidine kinase that is known to detect the antibiotic and then transduce this signal to the VanR transcription factor; however, fundamental questions remain about how exactly VanS senses vancomycin. Here, we focus on a purified VanRS system from one of the most clinically prevalent forms of VRE, type B. We show that in a native-like membrane environment, vancomycin strongly stimulates the autokinase activity of type-B VanS. We additionally demonstrate that this effect is mediated by a direct physical interaction between the antibiotic and the VanS periplasmic domain. This represents the first time that a direct sensing mechanism has been confirmed for any VanS protein from a human pathogen.","journal":"Journal of Biological Chemistry","year":2025,"id":566570,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1135124,"name":"Photis Rotsides","orcid":"0000-0003-2985-9954","position":1,"is_corresponding":false},{"id":1011818,"name":"Elizabeth J. D’Lauro","orcid":"0000-0001-6792-4521","position":2,"is_corresponding":false},{"id":1470221,"name":"Samantha Brady","orcid":"0009-0003-1367-1938","position":3,"is_corresponding":false},{"id":390877,"name":"Joris Beld","orcid":"0000-0001-7070-663X","position":4,"is_corresponding":false},{"id":574485,"name":"Patrick J. Loll","orcid":"0000-0001-5416-4500","position":5,"is_corresponding":false},{"id":773769,"name":"Lina Maciunas","orcid":"0000-0002-4430-9961","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":"40412528","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}