{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:58Z","timestamp":1792790518034,"version":"4.5.0"},"reference-count":40,"publisher":"Microbiology Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> \n                  <jats:italic>Trichosporon asahii<\/jats:italic> has been recognized as an opportunistic agent having a limited sensitivity to antifungal treatment.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold> Molecular mechanisms of azole resistance have been rarely reported for <jats:italic>Trichosproron asahii<\/jats:italic>. Similar to other fungi, we hypothesized that both <jats:italic>ERG11<\/jats:italic> gene mutation and efflux pumps genes hyper-expression were implicated.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Aim.<\/jats:bold> The current work aimed to study the sensitivity of clinical <jats:italic>T. asahii<\/jats:italic> isolates to different antifungal agents and to explore their resistance mechanisms by molecular methods including real-time PCR and gene sequencing.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods.<\/jats:bold> The sensitivity of <jats:italic>T. asahii<\/jats:italic> isolates to fluconazole, amphotericin B and voriconazole was estimated by the Etest method. Real-time PCR was used to measure the relative expression of <jats:italic>Pdr11, Mdr<\/jats:italic> and <jats:italic>ERG11<\/jats:italic> genes via the <jats:italic>ACT1<\/jats:italic> housekeeping gene. Three pairs of primers were also chosen to sequence the <jats:italic>ERG11<\/jats:italic> gene. This exploration was followed by statistical study including the receiver operating characteristic (ROC) curve analysis to identify a relationship between gene mean expression and the sensitivity of isolates.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> In 31 clinical isolates, the resistance frequencies were 87, 16.1 and 3.2\u200a%, respectively, for amphotericin B, fluconazole and voriconazole. Quantitative real-time PCR demonstrated that only <jats:italic>Mdr<\/jats:italic> over-expression was significantly associated with FCZ resistance confirmed by univariate statistical study and the ROC curve analysis (<jats:italic>P<\/jats:italic> &lt;0.05). The <jats:italic>ERG11<\/jats:italic> sequencing revealed two mutations H380G and S381A in TN325U11 (MIC FCZ=8\u2009\u00b5g ml<jats:sup>\u22121<\/jats:sup>) and H437R in TN114U09 (MIC FCZ=256\u2009\u00b5g ml<jats:sup>\u22121<\/jats:sup>) in highly conserved regions (close to the haem-binding domain) but their involvement in the resistance mechanism has not yet been assigned.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> \n                  <jats:italic>T. asahii<\/jats:italic> FCZ resistance mechanisms are proven to be much more complex and gene alteration sequence and\/or expression can be involved. Only <jats:italic>Mdr<\/jats:italic> gene over-expression was significantly associated with FCZ resistance and no good correlation was observed between FCZ and VCZ MIC values and relative gene expression. <jats:italic>ERG11<\/jats:italic> sequence alteration seems to play a major role in <jats:italic>T. asahii<\/jats:italic> FCZ resistance mechanism but their involvement needs further confirmation.<\/jats:p>","DOI":"10.1099\/jmm.0.001236","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T17:15:47Z","timestamp":1615396547000},"source":"Crossref","is-referenced-by-count":7,"title":["Implication of efflux pumps and ERG11 genes in resistance of clinical Trichosporon asahii isolates to fluconazole"],"prefix":"10.1099","volume":"70","author":[{"given":"S.","family":"Abbes","sequence":"first","affiliation":[{"name":"Fungal and Parasitic Molecular Biology Laboratory, School of Medicine, University of Sfax, Sfax, 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