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Previous studies demonstrated that several two\u2010component regulatory systems (TCSs) linked to the expression of lantibiotic transporters are involved in resistance to lantibiotics in\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    . In this study, we examined the susceptibility to four Class Ia bacteriocins (lantibiotics) among clinical isolates of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and sought to reveal the mechanisms underlying differences in susceptibility among strains. A direct assay was performed using nisin A, Pep5, nukacin ISK\u20101, and epidermin\u2010producing strains to examine the susceptibility of 149\n                    <jats:italic>S. aureus<\/jats:italic>\n                    isolates isolated from nasal cavity or bloodstream infections. Among them, some strains showed significantly higher susceptibility to epidermin, nukacin ISK\u20101, and nisin A. These strains did not show the induction of transporter\u2010encoded\n                    <jats:italic>vraD<\/jats:italic>\n                    expression in the presence of nisin A, suggesting impaired TCS BraRS function. Some strains harbored frameshifts or nonsense mutations in\n                    <jats:italic>braR<\/jats:italic>\n                    ,\n                    <jats:italic>braA<\/jats:italic>\n                    , and\n                    <jats:italic>braB<\/jats:italic>\n                    or the absence of transporter\u2010encoded\n                    <jats:italic>vraDEH<\/jats:italic>\n                    genes. In addition, strains with frameshifts in TCS GraR and transporter VraG genes showed increased susceptibility to nisin A, Pep5, and nukacin ISK\u20101. When comparing the susceptibility among MLST\u2010defined clonal complexes (CCs), CC45 showed higher susceptibility to nisin A, Pep5, and nukacin ISK\u20101, while CC5 exhibited low susceptibility to them. CC45 also showed higher susceptibility within the BraRS\u2010disrupted strains. The net negative charge of the cell surface did not vary significantly among CCs, suggesting the involvement of factors other than BraRS and GraRS. These findings provide important insights for evaluating bacteriocins as novel antimicrobial agents against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/1348-0421.70056","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:00:58Z","timestamp":1776060058000},"page":"268-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distribution of Lantibiotic Susceptibility and Its Association With Two\u2010Component Regulatory Systems in\n                    <i>Staphylococcus aureus<\/i>\n                    Clinical Isolates"],"prefix":"10.1111","volume":"70","author":[{"given":"Airi","family":"Odawara","sequence":"first","affiliation":[{"name":"Department of Bacteriology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"},{"name":"Department of Oral Oncology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4406-9718","authenticated-orcid":false,"given":"Yujin","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"},{"name":"Antimicrobial Resistance Research Center, National Institute of Infectious Diseases Higashi Murayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Kawada\u2010Matsuo","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"},{"name":"Project Research Centre for Nosocomial Infectious Diseases Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-4203","authenticated-orcid":false,"given":"Junzo","family":"Hisatsune","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance Research Center, National Institute of Infectious Diseases Higashi Murayama Japan"},{"name":"Project Research Centre for Nosocomial Infectious Diseases Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Arai","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance Research Center, National Institute of Infectious Diseases Higashi Murayama Japan"},{"name":"Project Research Centre for Nosocomial Infectious Diseases Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yo","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance Research Center, National Institute of Infectious Diseases Higashi Murayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyuki","family":"Sugai","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance Research Center, National Institute of Infectious Diseases Higashi Murayama Japan"},{"name":"Project Research Centre for Nosocomial Infectious Diseases Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-8347","authenticated-orcid":false,"given":"Souichi","family":"Yanamoto","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-7649","authenticated-orcid":false,"given":"Hitoshi","family":"Komatsuzawa","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"},{"name":"Project Research Centre for Nosocomial Infectious Diseases Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13100677"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.13111"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68834"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00559-07"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-024-00778-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00644-6"},{"issue":"2","key":"e_1_2_11_8_1","first-page":"4","article-title":"Staphylococcal\u2010Produced Bacteriocins and Antimicrobial Peptides: Their Potential as Alternative Treatments for Staphylococcus aureus Infections","volume":"9","author":"Newstead L. 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