{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:33:59Z","timestamp":1775176439475,"version":"3.50.1"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            . Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg\/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for\n            <jats:italic>qac<\/jats:italic>\n            genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of\n            <jats:italic>qacA<\/jats:italic>\n            ,\n            <jats:italic>qacB<\/jats:italic>\n            ,\n            <jats:italic>qacC<\/jats:italic>\n            , and\n            <jats:italic>qacG<\/jats:italic>\n            genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only\n            <jats:italic>qacA<\/jats:italic>\n            and\n            <jats:italic>qacB<\/jats:italic>\n            increased the chlorhexidine mode MIC. Isolates with a wild-type\n            <jats:italic>norA<\/jats:italic>\n            promoter or mutations in the\n            <jats:italic>norA<\/jats:italic>\n            promoter had similar biocide MIC distributions; notably, not all clinical isolates with\n            <jats:italic>norA<\/jats:italic>\n            mutations were resistant to fluoroquinolones.\n            <jats:italic>In vitro<\/jats:italic>\n            efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of\n            <jats:italic>norA<\/jats:italic>\n            , but these were distinct from this region of the clinical isolates. Still, none of the\n            <jats:italic>in vitro<\/jats:italic>\n            mutants displayed fitness defects in a killing assay in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Galleria mellonella<\/jats:named-content>\n            larvae. In conclusion, our data provide an in-depth comparative overview on efflux in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current\n            <jats:italic>in vitro<\/jats:italic>\n            tests appear not to be suitable for predicting levels of resistance that are clinically relevant.\n          <\/jats:p>","DOI":"10.1128\/aac.00498-13","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T04:58:27Z","timestamp":1368507507000},"page":"3488-3497","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":106,"title":["Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus"],"prefix":"10.1128","volume":"57","author":[{"given":"Leonardo","family":"Furi","sequence":"first","affiliation":[{"name":"LAMMB, Dipartimento Biotecnologie, Universit\u00e0 di Siena, Siena, Italy"}]},{"given":"Maria Laura","family":"Ciusa","sequence":"additional","affiliation":[{"name":"LAMMB, Dipartimento Biotecnologie, Universit\u00e0 di Siena, Siena, Italy"}]},{"given":"Daniel","family":"Knight","sequence":"additional","affiliation":[{"name":"Quotient Bioresearch, Fordham, United Kingdom"}]},{"given":"Valeria","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"LAMMB, Dipartimento Biotecnologie, Universit\u00e0 di Siena, Siena, Italy"},{"name":"Quotient Bioresearch, Fordham, United Kingdom"}]},{"given":"Nadia","family":"Tocci","sequence":"additional","affiliation":[{"name":"LAMMB, Dipartimento Biotecnologie, Universit\u00e0 di Siena, Siena, Italy"}]},{"given":"Daniela","family":"Cirasola","sequence":"additional","affiliation":[{"name":"Department of Public Health-Microbiology-Virology, Universit\u00e0 di Milano, Milan, Italy"}]},{"given":"Lluis","family":"Aragones","sequence":"additional","affiliation":[{"name":"Eurofins Biolab, Barcelona, Spain"}]},{"given":"Joana Rosado","family":"Coelho","sequence":"additional","affiliation":[{"name":"INESC-ID\/IST Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Ana Teresa","family":"Freitas","sequence":"additional","affiliation":[{"name":"INESC-ID\/IST Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Emmanuela","family":"Marchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Agrarie Universit\u00e0 di Firenze, Firenze, Italy"}]},{"given":"Laura","family":"Moce","sequence":"additional","affiliation":[{"name":"Eurofins Biolab, Barcelona, Spain"}]},{"given":"Pilar","family":"Visa","sequence":"additional","affiliation":[{"name":"Eurofins Biolab, Barcelona, Spain"}]},{"given":"John Blackman","family":"Northwood","sequence":"additional","affiliation":[{"name":"Quotient Bioresearch, Fordham, United Kingdom"}]},{"given":"Carlo","family":"Viti","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Agrarie Universit\u00e0 di Firenze, Firenze, Italy"}]},{"given":"Elisa","family":"Borghi","sequence":"additional","affiliation":[{"name":"Department of Public Health-Microbiology-Virology, Universit\u00e0 di Milano, Milan, Italy"}]},{"given":"Graziella","family":"Orefici","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Roma, Italy"}]},{"name":"the BIOHYPO Consortium","sequence":"additional","affiliation":[]},{"given":"Ian","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Quotient Bioresearch, Fordham, United Kingdom"}]},{"given":"Marco Rinaldo","family":"Oggioni","sequence":"additional","affiliation":[{"name":"LAMMB, Dipartimento Biotecnologie, Universit\u00e0 di Siena, Siena, Italy"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Directive 98\/8\/EC concerning the placing of biocidal products on the market","volume":"123","author":"European Parliament and Council","year":"1998","unstructured":"European Parliament and Council. 1998. 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