Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris.

Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris.
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进化枝特异性的染色体重排和念珠菌中亚电体粘附素的丧失。

DOI:
10.1093/genetics/iyab029
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发表时间:
2021-05-17
期刊:
影响因子:
3.3
通讯作者:
Cuomo CA
Cuomo CA
中科院分区:
生物学2区
文献类型:
--
作者:
Muñoz JF;Welsh RM;Shea T;Batra D;Gade L;Howard D;Rowe LA;Meis JF;Litvintseva AP;Cuomo CA

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耳念珠菌是一种新兴的真菌病原体,由于全球传播,能够引起医疗保健相关的爆发和抗真菌药物耐药性,引起了越来越多的关注。基因组分析显示,早期同时检测到的C。在地理上,奥里斯被分成四个主要分支。虽然进化枝I、III和IV负责持续的侵袭性和多药耐药感染的爆发,但进化枝II,也称为东亚进化枝,主要由耳部感染病例组成,通常对所有抗真菌药物敏感,并且与爆发无关。在这里,我们产生的染色体水平的组件代表这四个分支的系统发育的广度和唯一的隔离描述到目前为止,从进化枝V。这进化枝V基因组是高度同线的进化枝I,III和IV,虽然序列是高度发散的其他进化枝。进化枝II基因组出现高度重排,易位发生在GC贫乏区域附近,并且大多数染色体中存在大的亚端粒缺失,从而导致实质上不同的核型。重排和缺失长度在进化枝II分离株中各不相同,包括来自单个患者的两个,支持正在进行的基因组不稳定性。端粒下区富含Hyr/Iff样细胞表面蛋白、新的候选细胞壁蛋白和ALS样粘附素。来自这些家族的细胞壁蛋白和其他药物相关基因在进化枝I、III和IV中显示出进化枝特异性选择特征。亚端粒动力学和保守的细胞表面蛋白的进化枝负责全球爆发引起侵入性感染的解释进化枝之间观察到的不同表型。
Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.
机会性病原体念珠菌中基因组变异的模式表明,交配的存在和与人类的二次关联。
DOI: 10.1016/j.cub.2017.11.027
发表时间: 2018-01-08
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影响因子: 56.3
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影响因子: 11.1
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