{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:26Z","timestamp":1785430466026,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002865","name":"Chongqing Science and Technology Commission","doi-asserted-by":"crossref","award":["CSTB2022NSCQ-MSX1330"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1330"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CSTB2022NSCQ-MSX1330"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1330"]}],"id":[{"id":"https:\/\/ror.org\/05w9erc61","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) threatens the efficacy of this last-line antibiotic. The GraSR two-component system is frequently mutated in VISA strains. Here, we demonstrate that the GraS(T136I) point mutation, identified in the clinical VISA isolate XN108, is a key determinant of reduced vancomycin susceptibility. Introducing this mutation into the susceptible strain Newman increased the vancomycin MIC from 1.5 to 4 mg\/L, while its reversion in XN108 decreased the MIC from 12 to 8 mg\/L. The mutation conferred common phenotypes, including thickened cell wall, decreased autolysis, and reduced cell surface negative charge via upregulation of the dltABCD operon and mprF. Notably, the GraS(T136I) mutation also upregulated virulence genes (efb, hlb, sbi, hld) and enhanced hemolytic activity. Interestingly, despite this hypervirulent profile, the mutant showed impaired long-term survival within macrophages. Our study reveals that a single GraSR mutation can co-regulate vancomycin resistance and virulence, offering new insights into the adaptation of S. aureus to antibiotic pressure.<\/jats:p>","DOI":"10.3390\/microorganisms14051151","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:17:23Z","timestamp":1779203843000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Single Point Mutation in GraS Drives Co-Evolution of Vancomycin Resistance and Virulence in Staphylococcus aureus"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhen","family":"Hu","sequence":"first","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuwen","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilong","family":"Shang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5828-8764","authenticated-orcid":false,"given":"Huagang","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41579-025-01226-2","article-title":"Methicillin-resistant and susceptible Staphylococcus aureus: Tolerance, immune evasion and treatment","volume":"24","author":"Parsons","year":"2026","journal-title":"Nat. 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