Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris.
Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris.
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作者：
耳念珠菌作为一种人类真菌病原体仅在过去十年中出现。值得注意的是，C。耳炎病毒表现出高度的基因组多样性和表型可塑性，有四个主要分支引起医院爆发，死亡率和发病率很高。C.耳可显示对所有类别的抗真菌药物的临床抗性，包括通常被推荐作为侵袭性念珠菌病的一线疗法的棘白菌素。在这里，我们利用转录组学结合表型分析来表征一组临床C。显示出明显的棘白菌素抗性（ECN-R）的耳分离株。棘白菌素FKS 1靶基因的热点突变存在于所有耐药菌株中。此外，ECN-R菌株共享在ECN-R分离株中差异表达的362个基因的核心特征集。其中，线粒体基因表达和影响细胞壁功能的基因似乎是最突出的，后者与增强的粘附性状，增加细胞壁甘露聚糖含量，改变ECN-R菌株对细胞壁应激的敏感性相关。此外，ECN-R表型特征也与病原体识别和与免疫细胞的相互作用有关。因此，转录组学与表型配对是一个合适的工具，以预测抗性和健身性状，以及治疗结果的病原体群体具有复杂的表型多样性。
Candida auris emerged as a human fungal pathogen only during the past decade. Remarkably, C. auris displays high degrees of genomic diversity and phenotypic plasticity, with four major clades causing hospital outbreaks with high mortality and morbidity rates. C. auris can show clinical resistance to all classes of antifungal drugs, including echinocandins that are usually recommended as first-line therapies for invasive candidiasis. Here, we exploit transcriptomics coupled with phenotypic profiling to characterize a set of clinical C. auris isolates displaying pronounced echinocandin resistance (ECN-R). A hot spot mutation in the echinocandin FKS1 target gene is present in all resistant isolates. Moreover, ECN-R strains share a core signature set of 362 genes differentially expressed in ECN-R isolates. Among others, mitochondrial gene expression and genes affecting cell wall function appear to be the most prominent, with the latter correlating well with enhanced adhesive traits, increased cell wall mannan content, and altered sensitivity to cell wall stress of ECN-R isolates. Moreover, ECN-R phenotypic signatures were also linked to pathogen recognition and interaction with immune cells. Hence, transcriptomics paired with phenotyping is a suitable tool to predict resistance and fitness traits as well as treatment outcomes in pathogen populations with complex phenotypic diversity.
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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
影响因子：
6.7
作者：
Blankenship JR;Fanning S;Hamaker JJ;Mitchell AP
通讯作者：
Mitchell AP
影响因子：
6.4
作者：
Arora P;Singh P;Wang Y;Yadav A;Pawar K;Singh A;Padmavati G;Xu J;Chowdhary A
通讯作者：
Chowdhary A
DOI：
10.3390/jof7090754
发表时间：
2021-09-13
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Carolus H;Jacobs S;Lobo Romero C;Deparis Q;Cuomo CA;Meis JF;Van Dijck P
通讯作者：
Van Dijck P
细胞壁蛋白质组的靶向变化会影响白色念珠菌形成单晶和多晶粒生物膜的能力。
影响因子：
6.7
作者：
Cabral V;Znaidi S;Walker LA;Martin-Yken H;Dague E;Legrand M;Lee K;Chauvel M;Firon A;Rossignol T;Richard ML;Munro CA;Bachellier-Bassi S;d'Enfert C
通讯作者：
d'Enfert C