Integrated Transcriptomic Analysis of Trichosporon Asahii Uncovers the Core Genes and Pathways of Fluconazole Resistance

dc.contributor.authorLi, Haitaoen_US
dc.contributor.authorWang, Congminen_US
dc.contributor.authorChen, Yongen_US
dc.contributor.authorZhang, Shaoqiangen_US
dc.contributor.authorYang, Rongyaen_US
dc.contributor.utdAuthorChen, Yongen_US
dc.description.abstractTrichosporon asahii (T. asahii) has emerged as a dangerous pathogen that causes rare but life-threatening infections. Its resistance to certain antifungal agents makes it difficult to treat, especially for patients undergoing long-term antibiotic therapy. In this study, we performed a series of fluconazole (FLC) perturbation experiments for two T. asahii strains, a clinical isolate stain CBS 2479 (T2) and an environmental isolate strain CBS 8904 (T8), to uncover potential genes and pathways involved in FLC resistance. We achieved 10 transcriptomes of T2 and T8 that were based on dose and time series of FLC perturbations. Systematic comparisons of the transcriptomes revealed 32 T2 genes and 25 T8 genes that are highly sensitive to different FLC perturbations. In both T2 and T8 strains with the phenotype of FLC resistance, the processes of oxidation-reduction and transmembrane transport were detected to be significantly changed. The antifungal susceptibility testing of FLC and penicillin revealed their resistance pathways are merged. Accumulated mutations were found in 564T2 and 225 T8 genes, including four highly mutated genes that are functionally related to the target of rapamycin complex (TOR). Our study provides abundant data towards genome-wide understanding of the molecular basis of FLC resistance in T. asahii.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorship"This work was supported in partial by National Natural Science Foundation of China (Grant Number 81472892, 61572358) and the Natural Science Foundation of Tianjin Science and Technology Committee (Grant Number 16JCYBJC23600)."en_US
dc.identifier.bibliographicCitationLi, Haitao, Congmin Wang, Yong Chen, Shaoqiang Zhang, et al. 2017. "Integrated transcriptomic analysis of Trichosporon asahii uncovers the core genes and pathways of fluconazole resistance." Scientific Reports 7, doi:10.1038/s41598-017-18072-9en_US
dc.publisherNature Publishing Groupen_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.sourceScientific Reports
dc.subjectDrug Resistance, Fungalen_US
dc.subjectAmino Acid Substitutionen_US
dc.subjectDrug Resistance, Microbialen_US
dc.subject14-alpha Demethylaseen_US
dc.subjectAspergillus fumigatusen_US
dc.subjectMolecular Mechanisms of Pharmacological Actionen_US
dc.subjectCandida albicansen_US
dc.titleIntegrated Transcriptomic Analysis of Trichosporon Asahii Uncovers the Core Genes and Pathways of Fluconazole Resistanceen_US


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