{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:06:07Z","timestamp":1761512767678},"reference-count":30,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T00:00:00Z","timestamp":1268611200000},"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":["J Bacteriol"],"published-print":{"date-parts":[[2010,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In this work, we report that flavohemoglobin contributes to the azole susceptibility of\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            . We first observed that deletion of the flavohemoglobin gene leads to an increase in the viability of imidazole-treated\n            <jats:italic>S. aureus<\/jats:italic>\n            cells and that reversion to the wild-type phenotype occurs upon expression of flavohemoglobin from a multicopy plasmid. Further spectroscopic analyses showed that miconazole, the most efficient azole antibiotic against\n            <jats:italic>S. aureus<\/jats:italic>\n            , ligates to heme of both oxidized and reduced flavohemoglobin. The binding of miconazole to oxidized flavohemoglobin, with an association constant of 1.7 \u00d7 10\n            <jats:sup>6<\/jats:sup>\n            M\n            <jats:sup>\u22121<\/jats:sup>\n            , typical of a tight, specific binding equilibrium, results in augmentation of the superoxide production by the enzyme. These results are corroborated by\n            <jats:italic>in vivo<\/jats:italic>\n            studies showing that imidazole-treated\n            <jats:italic>S. aureus<\/jats:italic>\n            cells expressing flavohemoglobin contain a larger amount of reactive oxygen species. Moreover, it was observed that the survival of miconazole-treated\n            <jats:italic>S. aureus<\/jats:italic>\n            internalized by murine macrophages is higher for cells lacking flavohemoglobin. Altogether, the present data revealed that in\n            <jats:italic>S. aureus<\/jats:italic>\n            , flavohemoglobin enhances the antimicrobial activity of imidazoles via an increase of intracellular oxidative stress.\n          <\/jats:p>","DOI":"10.1128\/jb.01378-09","type":"journal-article","created":{"date-parts":[[2010,1,23]],"date-time":"2010-01-23T03:03:24Z","timestamp":1264215804000},"page":"1527-1533","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Binding of Azole Antibiotics to\n            <i>Staphylococcus aureus<\/i>\n            Flavohemoglobin Increases Intracellular Oxidative Stress"],"prefix":"10.1128","volume":"192","author":[{"given":"Li\u0301gia S.","family":"Nobre","sequence":"first","affiliation":[{"name":"Instituto de Tecnologia Qui\u0301mica e Biolo\u0301gica, Universidade Nova de Lisboa, Av. da Repu\u0301blica (EAN), 2780-157 Oeiras, Portugal"}]},{"given":"Smilja","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qui\u0301mica e Biolo\u0301gica, Universidade Nova de Lisboa, Av. da Repu\u0301blica (EAN), 2780-157 Oeiras, Portugal"}]},{"given":"Ana Filipa N.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qui\u0301mica e Biolo\u0301gica, Universidade Nova de Lisboa, Av. da Repu\u0301blica (EAN), 2780-157 Oeiras, Portugal"}]},{"given":"Eric","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Centre for Biophysics and Computational Biology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801"}]},{"given":"Peter","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Technische Universita\u0308t Berlin, Institut fu\u0308r Chemie, Sekr. PC14, Stra\u00dfe des 17. Juni 135, D-10623 Berlin, Germany"}]},{"given":"Miguel","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qui\u0301mica e Biolo\u0301gica, Universidade Nova de Lisboa, Av. da Repu\u0301blica (EAN), 2780-157 Oeiras, Portugal"}]},{"given":"Li\u0301gia M.","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qui\u0301mica e Biolo\u0301gica, Universidade Nova de Lisboa, Av. da Repu\u0301blica (EAN), 2780-157 Oeiras, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"22272","DOI":"10.1074\/jbc.M301285200","volume":"278","year":"2003","unstructured":"Bonamore, A., P. Gentili, A. Ilari, M. E. Schinina, and A. Boffi. 2003. Escherichia coli flavohemoglobin is an efficient alkylhydroperoxide reductase. J. Biol. Chem. 278 : 22272-22277.","journal-title":"J. Biol. 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