Genomic and transcriptome identification of fluconazole-resistant genes for Trichosporon asahii.
Genomic and transcriptome identification of fluconazole-resistant genes for Trichosporon asahii.
复制标题
旭毛孢子菌氟康唑耐药基因的基因组和转录组鉴定。
DOI：
10.1093/mmy/myz088
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Rong
中科院分区：
文献类型：
--
作者：
Zhikuan Xia;Haiying Yu;Congmin Wang;Xiao Ding;Dequan Zhang;Xinyu Tan;Jianghan Chen;Songnian Hu;Rong
阿萨希毛孢子菌感染在临床上很难控制。这项研究确定了一个超过15年的T。Asahii感染相关的系统性播散疾病，并进行基因组和转录组测序，以鉴定从该患者面部皮肤病变分离的氟康唑耐药菌株与敏感菌株中的氟康唑耐药基因。这些数据揭示了T.在氟康唑耐药株的asahii基因组中发现了36个新的ERG 11基因突变，ERG 3基因有3个点突变（V458 L、D457 V和D334 S），ERG 5基因有1个错义突变（E349 D）。Asahii基因组。为了确保ERG 11是负责氟康唑耐药性，因此，我们同时培养的菌株在体外和克隆的ERG 11 CDS序列的氟康唑敏感和耐药菌株到酿酒酵母。这些实验证实了ERG 11基因的这些突变影响了酿酒酵母中氟康唑的抗性（氟康唑抗性菌株和敏感菌株之间的MIC值> 64 μg/ml vs. <8 μg/ml）。此外，麦角甾醇生物合成途径基因和药物转运蛋白的表达在氟康唑耐药菌株中上调。朝平。总的来说，该女性患者的氟康唑耐药与ERG 11、ERG 3和ERG 5突变以及药物转运蛋白和脂肪酸代谢基因的差异表达相关。
Trichosporon asahii infection is difficult to control clinically. This study identified a case with over 15 years of T. asahii infection-related systemic dissemination disease and conducted genome and transcriptome sequencing to identify fluconazole-resistant genes in fluconazole-resistant versus susceptible strains isolated from this patient's facial skin lesions. The data revealed mutations of the ergosterol biosynthetic pathway-related genes in the T. asahii genome of the fluconazole-resistant strain, that is, there were 36 novel mutations of the ERG11 gene, three point mutations (V458L, D457V, and D334S) in the ERG3, and a missense mutation (E349D) in ERG5 in the fluconazole-resistant strain of the T. asahii genome. To ensure that ERG11 is responsible for the fluconazole resistance, we thus simultaneously cultured the strains in vitro and cloned the ERG11 CDS sequences of both fluconazole-susceptible and -resistant strains into the Saccharomyces cerevisiae. These experiments confirmed that these mutations of ERG11 gene affected fluconazole resistance (> 64 μg/ml vs. <8 μg/ml of the MIC value between fluconazole-resistant and -susceptible strains) in Saccharomyces cerevisiae. In addition, expression of ergosterol biosynthesis pathway genes and drug transporter was upregulated in the fluconazole-resistant strain of T. asahii. Collectively, the fluconazole resistance in this female patient was associated with mutations of ERG11, ERG3, and ERG5 and the differential expression of drug transporter and fatty acid metabolic genes.