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基因组视角下的耳念珠菌及其相关新兴种属的多药耐药性、交配和毒力。

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

机构信息

Broad Institute of MIT and Harvard, Cambridge, MA, 02144, USA.

Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, 30333, GA, USA.

出版信息

Nat Commun. 2018 Dec 17;9(1):5346. doi: 10.1038/s41467-018-07779-6.

Abstract

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 MTLα 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.

摘要

耳念珠菌是一种新兴的多药耐药真菌病原体,其暴发的报道越来越多。虽然与白念珠菌和光滑念珠菌关系较远,但耳念珠菌与罕有观察到且通常具有多药耐药性的 C. haemulonii 进化枝中的物种密切相关。在这里,我们分析了四个耳念珠菌进化枝和三个相关物种的近完整基因组组装,并绘制了七个染色体上的种内和种间重排。使用 RNA-Seq 指导的基因预测,我们发现大多数交配和减数分裂基因是保守的,并且进化枝包含 MTLa 或 MTLα 交配位点。将这些新兴物种的基因组与其他念珠菌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,包括扩展的转运体和脂肪酶家族,以及 ERG11 中的突变和拷贝数变异。基因表达分析确定了耳念珠菌特有的转运体和代谢调节剂,以及与相关物种保守的基因,这些可能导致这个新兴真菌进化枝在药物反应上的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad81/6297351/a076e8c94b41/41467_2018_7779_Fig1_HTML.jpg

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