| Title | Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans |
| Authors | Gong, Jie Chen, Xin-Fei Fan, Xin Xu, Juan Zhang, Han Li, Ruo-Yu Chen, Sharon C-A Kong, Fanrong Zhang, Shu Sun, Zi-Yong Kang, Mei Liao, Kang Guo, Da-Wen Wan, Zhe Hu, Zhi-Dong Chu, Yun-Zhuo Zhao, Hong-Mei Zou, Gui-Ling Shen, Chong Geng, Yuan-Yuan Wu, Wei-Wei Wang, He Zhao, Fei Lu, Xin He, Li-Hua Liu, Gui-Ming Xu, Ying-Chun Zhang, Jian-Zhong Xiao, Meng |
| Affiliation | Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Lab Med, Sate Key Lab Complex Severe & Rare Dis, Beijing, Peoples R China Beijing Key Lab Mech Res & Precis Diag Invas Fung, Beijing, Peoples R China Capital Med Univ, Beijing Inst Resp Med, Dept Infect Dis & Clin Microbiol, Beijing, Peoples R China Capital Med Univ, Beijing Chao Yang Hosp, Beijing, Peoples R China Beijing Univ First Hosp, Dept Dermatol, Beijing, Peoples R China Beijing Key Lab Mol Diag Dermatoses, Beijing, Peoples R China Beijing Univ, Res Ctr Med Mycol, Beijing, Peoples R China Univ Sydney, Westmead Hosp, Inst Clin Pathol & Med Res, Ctr Infect Dis & Microbiol Lab Serv,New South Wal, Sydney, NSW, Australia Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Clin Lab, Wuhan, Hubei, Peoples R China Sichuan Univ, West China Hosp, Dept Lab Med, Chengdu, Sichuan, Peoples R China Sun Yat Sen Univ, Affiliated Hosp 1, Dept Clin Lab, Guangzhou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Dept Clin Lab, Harbin, Heilongjiang, Peoples R China Tianjin Med Univ Gen Hosp, Dept Clin Lab, Tianjin, Peoples R China China Med Univ, Hosp 1, Dept Clin Lab, Shenyang, Liaoning, Peoples R China Peoples Hosp Liaoning Prov, Dept Clin Lab, Shenyang, Liaoning, Peoples R China Harbin Med Univ, Affiliated Hosp 4, Dept Clin Lab, Harbin, Heilongjiang, Peoples R China Tsinghua Univ, Ctr Stat Sci, Beijing, Peoples R China Tsinghua Univ, Dept Ind Engn, Beijing, Peoples R China Fifth Peoples Hosp Hainan Prov, Dept Dermatol, Haikou, Hainan, Peoples R China Beijing Key Lab Mech Res & Precis Diag Invas Fung, Dynamiker Sub Ctr, Tianjin, Peoples R China Beijing Acad Agr & Forestry Sci, Beijing Agro Biotechnol Res Ctr, Beijing, Peoples R China |
| Keywords | AZOLE RESISTANCE MOLECULAR PHYLOGENETICS ERG11 MUTATIONS FLUCONAZOLE GENES IDENTIFICATION EPIDEMIOLOGY FLUCYTOSINE EXPRESSION ALGORITHM |
| Issue Date | Jan-2023 |
| Publisher | MICROBIOLOGY SPECTRUM |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/672709 |
| ISSN | 2165-0497 |
| DOI | 10.1128/spectrum.03807-22 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
