关键词: Candida auris Erg 11 mutation K143R azole resistance pan-genome analysis phylogenomics whole genome sequencing (WGS)

来  源:   DOI:10.3390/jof10060392   PDF(Pubmed)

Abstract:
Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes (ERG11 and FKS1) associated with drug resistance in C. auris, a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.
摘要:
耳念珠菌是一种新兴的多重耐药和机会致病酵母。全基因组测序分析已经定义了五个主要分支,每个都来自不同的地理区域。当前的研究旨在检查C.auris20-1498菌株的基因组,这是墨西哥发现的这种真菌的第一个分离株。基于全基因组测序,基因组草图被发现包含70个重叠群。它的总基因组大小为12.86Mbp,N50值为1.6Mbp,鸟嘌呤-胞嘧啶(GC)的平均含量为45.5%。基因组注释显示共有5432个基因编码5515种蛋白质。根据基因组分析,C.auris20-1498菌株属于进化枝IV(包含南美特有的菌株)。在与金黄色葡萄球菌耐药相关的两个基因(ERG11和FKS1)中,在K143R中检测到一个突变,位于ERG11(羊毛甾醇14-α-脱甲基酶)突变热点的基因,抗真菌药物靶标。全基因组测序和鉴定与真菌耐药性相关的突变可能导致发现新的治疗靶标和新的抗真菌化合物。
公众号