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Due to the extensive application of antibiotics,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      has developed resistance to antibiotics, especially vancomycin, making clinical treatment challenging. Staphylococcal accessory regulator A (SarA) modulates\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      virulence by regulating the principal virulence factors. However, its role in vancomycin resistance remains largely unknown. Herein, we found that SarA not only reduces the susceptibility of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to vancomycin by directly inhibiting the expression of autolysis-related genes, but also enhances resistance to vancomycin by negatively regulating the transcription of an ATP-binding cassette (ABC) transporter, ABC-like, thereby altering the bacterial surface charge and reducing vancomycin\u2019s binding efficiency to the cell wall. Moreover, the regulation of antibiotic resistance by SarA is strain-dependent. Our study uncovers the roles of SarA in regulating vancomycin resistance, providing potential targets and ideas for the prevention and control of vancomycin-intermediate\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        poses a major threat to public health due to its increasing resistance to vancomycin, a last-line antibiotic. This study reveals that Staphylococcal accessory regulator A regulates vancomycin resistance in\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        by suppressing genes related to autolysis and negatively regulating an ATP-binding cassette (ABC) transporter (ABC-like). This regulation of the transporter reduces the bacterial surface charge, impairing the ability of vancomycin to bind to the cell wall. These findings suggest a novel mechanism of antibiotic resistance in\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        and identify potential targets for combating vancomycin-intermediate\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01630-25","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T13:00:51Z","timestamp":1770642051000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Staphylococcal accessory regulator SarA-mediated modulation of autolysis and surface charge enables\n                    <i>Staphylococcus aureus<\/i>\n                    to evade vancomycin killing"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9293-6233","authenticated-orcid":true,"given":"Yujie","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02njz9p87","id-type":"ROR","asserted-by":"publisher"}],"name":"Anhui Province Key Laboratory of Pollution Damage and Biological Control for Huaihe River Basin, School of Biological and Food Engineering, Fuyang Normal University","place":["Fuyang, China"]},{"id":[{"id":"https:\/\/ror.org\/02njz9p87","id-type":"ROR","asserted-by":"publisher"}],"name":"Anhui Province Key Laboratory of Embryo Development and Reproduction Regulation, School of Biological and Food Engineering, Fuyang Normal University","place":["Fuyang, China"]},{"id":[{"id":"https:\/\/ror.org\/02njz9p87","id-type":"ROR","asserted-by":"publisher"}],"name":"Anhui Province Key Laboratory of Environmental Hormone and Reproduction, School of Biological and Food Engineering, Fuyang Normal 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