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In the food industry, there is an increasing prevalence of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      despite the widespread use of antimicrobial preservatives, and it remains elusive how WTAs affect the susceptibility of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to these preservatives. In this study, we first identified that the presence of WTAs altered\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      sensitivity to tea polyphenol, sodium dehydroacetate, and \u03b5-polylysine after screening 14 frequently used antimicrobial food preservatives. Then, via a series of genetic and biochemical analyses combined with molecular dynamics simulation, we revealed three WTA-related mechanisms adopted by\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      for self-protection against sodium dehydroacetate and \u03b5-polylysine: (i) charge repulsion mediated by D-alanylation to reduce preservative packing around the cell; (ii) hydrogen bonding and hydrophobic interactions involving WTA backbone and glycosylation to maintain the preservatives in the WTA layer and to reduce their passage across the cell membrane; (iii) steric hindrance to reduce cell wall permeability and minimize the contact of these antimicrobials with the cell membrane. In comparison, the latter two mechanisms were involved in cell interaction with tea polyphenol. This work highlights the complex roles played by WTAs in cell response to antimicrobial preservatives and provides guidance to further study on\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      tolerance to food preservatives and better control over food safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a disease-causing bacterium frequently detected in raw and packaged food that can be strongly insensitive to many bacteria-inhibiting or bacteria-killing agents. With the widespread use of antimicrobial food preservatives during food processing and packaging, there is a potential risk that these preservatives may force\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to become less sensitive. Given that\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      tolerates many antimicrobial agents using mechanisms related to wall teichoic acids (WTAs), the negatively charged polymers that are anchored in the cell wall of this bacterium, it is necessary to evaluate whether\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      presents WTA-dependent sensitivity to antimicrobial food preservatives and how WTAs affect\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      interaction with these preservatives. Our study answered these questions for tea polyphenol, sodium dehydroacetate, and \u03b5-polylysine and revealed three WTA-related mechanisms including charge repulsion, surface trapping, and decline in cell wall permeability. This work emphasizes the need for further control over food safety.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01023-25","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T09:00:28Z","timestamp":1751274028000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Mechanistic study on the susceptibility of\n                    <i>Staphylococcus aureus<\/i>\n                    to common antimicrobial preservatives mediated by wall teichoic acids"],"prefix":"10.1128","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4161-6552","authenticated-orcid":false,"given":"Xia","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05s32j989","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Food Science and Engineering, School of Biological and Pharmaceutical Sciences, Shaanxi University of 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