{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:44:01Z","timestamp":1790639041830,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRF\u2010ISF003\u20103039\/19"],"award-info":[{"award-number":["NRF\u2010ISF003\u20103039\/19"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Invasive candidiasis caused by non\u2010<jats:italic>albicans<\/jats:italic> species has been on the rise, with <jats:italic>Candida glabrata<\/jats:italic> emerging as the second most common etiological agent. <jats:italic>Candida glabrata<\/jats:italic> possesses an intrinsically lower susceptibility to azoles and an alarming propensity to rapidly develop high\u2010level azole resistance during treatment. In this study, we have developed an efficient <jats:italic>piggyBac<\/jats:italic> (<jats:italic>PB<\/jats:italic>) transposon\u2010mediated mutagenesis system in <jats:italic>C. glabrata<\/jats:italic> to conduct genome\u2010wide genetic screens and applied it to profile genes that contribute to azole resistance. When challenged with the antifungal drug fluconazole, <jats:italic>PB<\/jats:italic> insertion into 270 genes led to significant resistance. A large subset of these genes has a role in the mitochondria, including almost all genes encoding the subunits of the F<jats:sub>1<\/jats:sub>F<jats:sub>0<\/jats:sub> ATPase complex. We show that deleting <jats:italic>ATP3<\/jats:italic> or <jats:italic>ATP22<\/jats:italic> results in increased azole resistance but does not affect susceptibility to polyenes and echinocandins. The increased azole resistance is due to increased expression of <jats:italic>PDR1<\/jats:italic> that encodes a transcription factor known to promote drug efflux pump expression. Deleting <jats:italic>PDR1<\/jats:italic> in the <jats:italic>atp3<\/jats:italic>\u0394 or <jats:italic>atp22<\/jats:italic>\u0394 mutant resulted in hypersensitivity to fluconazole. Our results shed light on the mechanisms contributing to azole resistance in <jats:italic>C. glabrata<\/jats:italic>. This <jats:italic>PB<\/jats:italic> transposon\u2010mediated mutagenesis system can significantly facilitate future genome\u2010wide genetic screens.<\/jats:p>","DOI":"10.1111\/mmi.15229","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T03:49:00Z","timestamp":1705722540000},"page":"781-797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genome\u2010wide profiling of <scp><i>piggyBac<\/i><\/scp> transposon insertion mutants reveals loss of the <scp>F<sub>1<\/sub>F<sub>0<\/sub> ATPase<\/scp> complex causes fluconazole resistance in <i>Candida glabrata<\/i>"],"prefix":"10.1111","volume":"121","author":[{"given":"Eve W. 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