Transcriptome Signatures Predict Phenotypic Variations of Candida auris.
Transcriptome Signatures Predict Phenotypic Variations of Candida auris.
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DOI：
10.3389/fcimb.2021.662563
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发表时间：
2021
影响因子：
5.7
通讯作者：
Kuchler K
中科院分区：
文献类型：
--
作者：
Jenull S;Tscherner M;Kashko N;Shivarathri R;Stoiber A;Chauhan M;Petryshyn A;Chauhan N;Kuchler K
卫生保健设施正面临着最近出现的人类真菌病原体耳念珠菌的严重威胁，由于其显着的抗真菌多药耐药性和诊断工具差。独特的C。auris进化枝似乎在独立的地理位置同时进化，并显示遗传和表型多样性。虽然比较基因组学和表型分析研究不断增加，但我们仍然缺乏对C。耳的物种多样性和临床异质性。由于基因表达变异性影响表型可塑性，我们的目的是表征C。耳患者分离株具有不同的抗真菌药敏谱。首先，我们对临床分离的念珠菌进行了抗真菌药敏试验。auris分离株，以确定不同的分支内的抗真菌治疗反应。有趣的是，比较转录谱揭示了大的基因表达差异的进化枝I菌株和一个进化枝II菌株，无论他们的抗真菌药。然而，在进化枝水平的比较表明，基因表达的微小变化足以驱动不同的药物反应。最后，我们在功能上验证了反映临床分离株表型差异的转录特征。因此，我们的研究结果表明，大规模的转录谱允许预测患者分离株的表型差异，这可能有助于选择合适的抗真菌治疗的多重耐药念珠菌。耳。
Health care facilities are facing serious threats by the recently emerging human fungal pathogen Candida auris owing to its pronounced antifungal multidrug resistance and poor diagnostic tools. Distinct C. auris clades evolved seemingly simultaneously at independent geographical locations and display both genetic and phenotypic diversity. Although comparative genomics and phenotypic profiling studies are increasing, we still lack mechanistic knowledge about the C. auris species diversification and clinical heterogeneity. Since gene expression variability impacts phenotypic plasticity, we aimed to characterize transcriptomic signatures of C. auris patient isolates with distinct antifungal susceptibility profiles in this study. First, we employed an antifungal susceptibility screening of clinical C. auris isolates to identify divergent intra-clade responses to antifungal treatments. Interestingly, comparative transcriptional profiling reveals large gene expression differences between clade I isolates and one clade II strain, irrespective of their antifungal susceptibilities. However, comparisons at the clade levels demonstrate that minor changes in gene expression suffice to drive divergent drug responses. Finally, we functionally validate transcriptional signatures reflecting phenotypic divergence of clinical isolates. Thus, our results suggest that large-scale transcriptional profiling allows for predicting phenotypic diversities of patient isolates, which may help choosing suitable antifungal therapies of multidrug-resistant C. auris.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
酵母中种内转录组内景观的演变。
影响因子：
14.9
作者：
Brion C;Pflieger D;Friedrich A;Schacherer J
通讯作者：
Schacherer J
影响因子：
3.4
作者：
Abe, Fumiyoshi;Hiraki, Toshiki
通讯作者：
Hiraki, Toshiki
影响因子：
3
作者：
Bernardo, Stella M.;Khalique, Zachary;Lee, Samuel A.
通讯作者：
Lee, Samuel A.
影响因子：
56.3
作者：
Chow, Nancy A.;Gade, Lalitha;Litvintseva, Anastasia P.
通讯作者：
Litvintseva, Anastasia P.