Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species

Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species
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DOI:
10.1038/s41467-018-07779-6
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发表时间:
2018-12-17
影响因子:
16.6
通讯作者:
Cuomo, Christina A.
Cuomo, Christina A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Munoz, Jose F.;Gade, Lalitha;Cuomo, Christina A.

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耳念珠菌是一种新兴的多重耐药真菌病原体,引起越来越多的报告暴发。虽然与C.白色念珠菌和C.光叶C. auris与C. Haemulonii分支在这里,我们分析了近完整的基因组组装的四个C。auris进化枝和三个相关物种,并绘制跨七条染色体的种内和种间重排。使用RNA-Seq引导的基因预测,我们发现大多数交配和减数分裂基因是保守的,并且分支包含MTLa或MTL α交配位点。将这些新兴物种的基因组与其他念珠菌属物种的基因组进行比较,确定了与耐药性和毒力相关的基因,包括转运蛋白和脂肪酶的扩展家族,以及ERG 11中的突变和拷贝数变异。基因表达分析鉴定了C.耳和那些保守的相关物种,这可能有助于在这个新兴的真菌分支的药物反应的差异。
Candida auris is an emergent multidrug-resistant fungal pathogen causing increasing reports of outbreaks. While distantly related to C. albicans and C. glabrata, C. auris is closely related to rarely observed and often multidrug-resistant species from the C. haemulonii clade. Here, we analyze near complete genome assemblies for the four C. auris clades and three related species, and map intra-and inter-species rearrangements across the seven chromosomes. Using RNA-Seq-guided gene predictions, we find that most mating and meiosis genes are conserved and that clades contain either the MTLa or MTL alpha mating loci. Comparing the genomes of these emerging species to those of other Candida species identifies genes linked to drug resistance and virulence, including expanded families of transporters and lipases, as well as mutations and copy number variants in ERG11. Gene expression analysis identifies transporters and metabolic regulators specific to C. auris and those conserved with related species which may contribute to differences in drug response in this emerging fungal clade.