{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:52:25Z","timestamp":1793145145244,"version":"4.5.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"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":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Mitochondrial dysfunction is one of the possible mechanisms by which azole resistance can occur in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida glabrata<\/jats:named-content>\n            . Cells with mitochondrial DNA deficiency (so-called \u201cpetite mutants\u201d) upregulate ATP binding cassette (ABC) transporter genes and thus display increased resistance to azoles. Isolation of such\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            mutants from patients receiving antifungal therapy or prophylaxis has been rarely reported. In this study, we characterized two sequential and related\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            isolates recovered from the same patient undergoing azole therapy. The first isolate (BPY40) was azole susceptible (fluconazole MIC, 4 \u03bcg\/ml), and the second (BPY41) was azole resistant (fluconazole MIC, &gt;256 \u03bcg\/ml). BPY41 exhibited mitochondrial dysfunction and upregulation of the ABC transporter genes\n            <jats:italic>C. glabrata CDR1<\/jats:italic>\n            (\n            <jats:italic>CgCDR1<\/jats:italic>\n            ),\n            <jats:italic>CgCDR2<\/jats:italic>\n            , and\n            <jats:italic>CgSNQ2<\/jats:italic>\n            . We next assessed whether mitochondrial dysfunction conferred a selective advantage during host infection by testing the virulence of BPY40 and BPY41 in mice. Surprisingly, even with\n            <jats:italic>in vitro<\/jats:italic>\n            growth deficiency compared to BPY40, BPY41 was more virulent (as judged by mortality and fungal tissue burden) than BPY40 in both systemic and vaginal murine infection models. The increased virulence of the petite mutant correlated with a drastic gain of fitness in mice compared to that of its parental isolate. To understand this unexpected feature, genome-wide changes in gene expression driven by the petite mutation were analyzed by use of microarrays during\n            <jats:italic>in vitro<\/jats:italic>\n            growth. Enrichment of specific biological processes (oxido-reductive metabolism and the stress response) was observed in BPY41, all of which was consistent with mitochondrial dysfunction. Finally, some genes involved in cell wall remodelling were upregulated in BPY41 compared to BPY40, which may partially explain the enhanced virulence of BPY41. In conclusion, this study shows for the first time that mitochondrial dysfunction selected\n            <jats:italic>in vivo<\/jats:italic>\n            under azole therapy, even if strongly affecting\n            <jats:italic>in vitro<\/jats:italic>\n            growth characteristics, can confer a selective advantage under host conditions, allowing the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            mutant to be more virulent than wild-type isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.01271-10","type":"journal-article","created":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T10:20:09Z","timestamp":1297765209000},"page":"1852-1860","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":139,"title":["Loss of Mitochondrial Functions Associated with Azole Resistance in Candida glabrata Results in Enhanced Virulence in Mice"],"prefix":"10.1128","volume":"55","author":[{"given":"S\u00e9l\u00e8ne","family":"Ferrari","sequence":"first","affiliation":[{"name":"Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Universit\u00e0 Cattolica Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"De Bernardis","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Torelli","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Universit\u00e0 Cattolica Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Posteraro","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Universit\u00e0 Cattolica Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Vandeputte","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Sanglard","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.07.002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.030072-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-49-11-977"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00215-08"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.3.847-853.2003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1788-1796.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki200"},{"key":"e_1_3_3_9_2","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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