Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans

文献类型： 外文期刊

第一作者： Gong, Jie

作者： Gong, Jie;Xu, Juan;Zhang, Shu;Geng, Yuan-Yuan;Zhao, Fei;Lu, Xin;He, Li-Hua;Zhang, Jian-Zhong;Chen, Xin-Fei;Zhang, Han;Xu, Ying-Chun;Xiao, Meng;Chen, Xin-Fei;Zhang, Han;Xu, Ying-Chun;Xiao, Meng;Fan, Xin;Fan, Xin;Li, Ruo-Yu;Wan, Zhe;Li, Ruo-Yu;Wan, Zhe;Li, Ruo-Yu;Chen, Sharon C-A;Kong, Fanrong;Sun, Zi-Yong;Kang, Mei;Liao, Kang;Guo, Da-Wen;Hu, Zhi-Dong;Chu, Yun-Zhuo;Zhao, Hong-Mei;Zou, Gui-Ling;Shen, Chong;Shen, Chong;Wu, Wei-Wei;Wang, He;Liu, Gui-Ming

作者机构：

关键词： Candida albicans; phylogenetic population; azole-resistance; Erg11p; Tac1p; azole-nonsusceptibility

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.7； 五年影响因子：5.9 ）

ISSN： 2165-0497

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-alpha, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-alpha isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-alpha isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones.IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns. Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat.

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