{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T18:40:43Z","timestamp":1769971243817,"version":"3.49.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Res Notes"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in <jats:italic>Staphylococcus aureus.<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Findings<\/jats:title>\n            <jats:p>\n              <jats:italic>LacZ<\/jats:italic> promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were <jats:italic>hla<\/jats:italic> and <jats:italic>spa<\/jats:italic> encoding \u03b1-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the <jats:italic>agr<\/jats:italic> quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of <jats:italic>S. aureus<\/jats:italic> to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, <jats:italic>hla<\/jats:italic> and <jats:italic>spa<\/jats:italic>. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the \u03b2-lactam sub-group cephalosporins enhanced expression of RNAIII and <jats:italic>hla<\/jats:italic> but diversely affected expression of <jats:italic>spa<\/jats:italic>. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate <jats:italic>spa<\/jats:italic>, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the <jats:italic>spa<\/jats:italic>-inducing cefalotin resulted in less biofilm formation compared to the <jats:italic>spa<\/jats:italic>-repressing cefotaxime.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We find that independently of the cephalosporin generation, cephalosporins oppositely regulate <jats:italic>spa<\/jats:italic> expression and biofilm formation. Repression of <jats:italic>spa<\/jats:italic> expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes <jats:italic>spa<\/jats:italic> expression independently of <jats:italic>agr<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-0500-5-457","type":"journal-article","created":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T18:14:06Z","timestamp":1345918446000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus"],"prefix":"10.1186","volume":"5","author":[{"given":"Lene N","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Roggenbuck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Haaber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Ifrah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne","family":"Ingmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,8,25]]},"reference":[{"issue":"Suppl 1","key":"1785_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1469-0691.2008.02682.x","volume":"15","author":"J Davies","year":"2009","unstructured":"Davies J: Everything depends on everything else. 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