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The global regulator\n                      <jats:italic>agr<\/jats:italic>\n                      is known as a well-described virulence regulator. Previous studies have found that\n                      <jats:italic>agr<\/jats:italic>\n                      -dysfunction strains are more likely to develop into vancomycin-resistant strains, but the mechanism for this phenomenon remains unknown. VraSR is a two-component regulatory system related to vancomycin resistance. In this study, we found that the expression levels of\n                      <jats:italic>vraR<\/jats:italic>\n                      were higher in\n                      <jats:italic>agr<\/jats:italic>\n                      -dysfunction clinical strains than in the\n                      <jats:italic>agr<\/jats:italic>\n                      -functional strains. We knocked out\n                      <jats:italic>agr<\/jats:italic>\n                      in a clinical strain, and quantitative reverse transcription PCR and \u03b2-galactosidase activity assays revealed that\n                      <jats:italic>agr<\/jats:italic>\n                      repressed transcription of\n                      <jats:italic>vraR<\/jats:italic>\n                      . After vancomycin exposures, population analysis revealed larger subpopulations displaying reduced susceptibility in\n                      <jats:italic>agr<\/jats:italic>\n                      knockout strain compared with wild-type strain, and this pattern was also observed in\n                      <jats:italic>agr<\/jats:italic>\n                      -dysfunction clinical strains compared with the\n                      <jats:italic>agr<\/jats:italic>\n                      -functional strains. Electrophoretic mobility experiment demonstrated binding of purified AgrA to the promoter region of\n                      <jats:italic>vraR<\/jats:italic>\n                      . In conclusion, our results indicated that the loss of\n                      <jats:italic>agr<\/jats:italic>\n                      function in\n                      <jats:italic>S. aureus<\/jats:italic>\n                      may contribute to the evolution of reduced vancomycin susceptibility through the downregulation of\n                      <jats:italic>vraSR<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00893-23","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T09:00:25Z","timestamp":1706000425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["AgrA directly binds to the promoter of\n                    <i>vraSR<\/i>\n                    and downregulates its expression in\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1128","volume":"68","author":[{"given":"Xueer","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 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