Integrated transcriptomic analysis of Trichosporon Asahii uncovers the core genes and pathways of fluconazole resistance.
Integrated transcriptomic analysis of Trichosporon Asahii uncovers the core genes and pathways of fluconazole resistance.
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整合转录组分析
DOI：
10.1038/s41598-017-18072-9
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发表时间：
2017-12-19
影响因子：
4.6
通讯作者：
Yang R
中科院分区：
文献类型：
--
作者：
Li H;Wang C;Chen Y;Zhang S;Yang R
Asahii（T. asahii）已经成为一种危险的病原体，引起罕见但危及生命的感染。它对某些抗真菌药物的耐药性使其难以治疗，特别是对于接受长期抗生素治疗的患者。在这项研究中，我们进行了一系列的干扰实验氟康唑（FLC）的两个T。asahii菌株、临床分离菌株CBS 2479（T2）和环境分离菌株CBS 8904（T8），以揭示涉及FLC抗性的潜在基因和途径。我们获得了10个T2和T8的转录组，这些转录组是基于FLC扰动的剂量和时间序列。转录组的系统比较显示32个T2基因和25个T8基因对不同的FLC扰动高度敏感。在具有FLC抗性表型的T2和T8菌株中，检测到氧化还原和跨膜转运过程的显著改变。FLC和青霉素的药敏试验显示它们的耐药途径是合并的。在564个T2和225个T8基因中发现了累积突变，其中包括4个与雷帕霉素复合物（TOR）靶点功能相关的高度突变基因。我们的研究提供了丰富的数据，对全基因组的理解的分子基础的FLC抗性在T。朝平。
Trichosporon 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 564 T2 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.
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DOI：
10.1126/science.aad3292
发表时间：
2016-01-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baym M;Stone LK;Kishony R
通讯作者：
Kishony R
影响因子：
3.7
作者：
Cobley D;Hálová L;Schauries M;Kaczmarek A;Franz-Wachtel M;Du W;Krug K;Maček B;Petersen J
通讯作者：
Petersen J
影响因子：
2.3
作者：
Choi, Kyoung Sub;Yoon, Sang Chul;Seo, Kyoung Yul
通讯作者：
Seo, Kyoung Yul
影响因子：
11.8
作者：
Alexander, Barbara D.;Johnson, Melissa D.;Pfaller, Michael A.
通讯作者：
Pfaller, Michael A.
影响因子：
120.1
作者：
Brown, David
通讯作者：
Brown, David