Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population

Xin Fan, Rong-Chen Dai, Shu Zhang, Yuan-Yuan Geng, Mei Kang, Da-Wen Guo, Ya-Ning Mei, Yu-Hong Pan, Zi-Yong Sun, Ying-Chun Xu (), Jie Gong () and Meng Xiao ()
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Xin Fan: Capital Medical University
Rong-Chen Dai: Chinese Academy of Medical Sciences
Shu Zhang: Chinese Center for Disease Control and Prevention
Yuan-Yuan Geng: Chinese Center for Disease Control and Prevention
Mei Kang: Sichuan University
Da-Wen Guo: First Affiliated Hospital of Harbin Medical University
Ya-Ning Mei: Jiangsu Province Hospital
Yu-Hong Pan: Fujian Medical University Union Hospital
Zi-Yong Sun: Tongji Medical College of Huazhong University of Science and Technology
Ying-Chun Xu: Chinese Academy of Medical Sciences
Jie Gong: Chinese Center for Disease Control and Prevention
Meng Xiao: Chinese Academy of Medical Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Invasive diseases caused by the globally distributed commensal yeast Candida tropicalis are associated with mortality rates of greater than 50%. Notable increases of azole resistance have been observed in this species, particularly within Asia-Pacific regions. Here, we carried out a genetic population study on 1571 global C. tropicalis isolates using multilocus sequence typing (MLST). In addition, whole-genome sequencing (WGS) analysis was conducted on 629 of these strains, comprising 448 clinical invasive strains obtained in this study and 181 genomes sourced from public databases. We found that MLST clade 4 is the predominant azole-resistant clone. WGS analyses demonstrated that dramatically increasing rates of azole resistance are associated with a rapid expansion of cluster AZR, a sublineage of clade 4. Cluster AZR isolates exhibited a distinct high-level azole resistance, which was induced by tandem duplications of the ERG11A395T gene allele. Ty3/gypsy-like retrotransposons were found to be highly enriched in this population. The alarming expansion of C. tropicalis cluster AZR population underscores the urgent need for strategies against growing threats of antifungal resistance.

Date: 2023
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DOI: 10.1038/s41467-023-43380-2

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