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Here we found that the cell-free supernatant of <jats:italic>Bacillus subtilis<\/jats:italic> (<jats:italic>B. subtilis<\/jats:italic> CFS) killed planktonic and biofilm <jats:italic>S. aureus<\/jats:italic>, and increased <jats:italic>S. aureus<\/jats:italic> susceptibility to penicillin and gentamicin as well. Further study showed that <jats:italic>B. subtilis<\/jats:italic> CFS suppressed the expression of the genes involved in adhesive molecules (<jats:italic>Cna<\/jats:italic> and <jats:italic>ClfA<\/jats:italic>), virulence factor <jats:italic>Hla<\/jats:italic>, quorum sensing (<jats:italic>argA<\/jats:italic>, <jats:italic>argB<\/jats:italic> and <jats:italic>RNAIII<\/jats:italic>) and biofilm formation (<jats:italic>Ica<\/jats:italic> and <jats:italic>sarA<\/jats:italic>) in <jats:italic>S. aureus<\/jats:italic>. Additionally, our data showed that <jats:italic>B. subtilis<\/jats:italic> CFS changed the membrane components and increased membrane permeabilization of <jats:italic>S. aureus<\/jats:italic>. Finally, we demonstrated that <jats:italic>B. subtilis<\/jats:italic> CFS increased considerably the susceptibility of <jats:italic>S. aureus<\/jats:italic> to penicillin and effectively reduced <jats:italic>S. aureus<\/jats:italic> burdens in a mouse model of implant-associated osteomyelitis. These findings support that <jats:italic>B. subtilis<\/jats:italic> CFS may be a potential resistance-modifying agent for \u03b2-lactam antibiotics against <jats:italic>S. aureus<\/jats:italic>.<\/jats:p>","DOI":"10.1186\/s12934-021-01592-5","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T20:04:41Z","timestamp":1621281881000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Bacillus subtilis revives conventional antibiotics against Staphylococcus aureus osteomyelitis"],"prefix":"10.1186","volume":"20","author":[{"given":"Fan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiluan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihuang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-5013","authenticated-orcid":false,"given":"Xianrong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"1592_CR1","first-page":"229","volume":"409","author":"EA Idelevich","year":"2017","unstructured":"Idelevich EA, Kreis C, L\u00f6ffler B, Peters G. 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