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

Author

Listed:
  • Xin Fan

    (Capital Medical University
    Chinese Academy of Medical Sciences)

  • Rong-Chen Dai

    (Chinese Academy of Medical Sciences
    Chinese Center for Disease Control and Prevention)

  • Shu Zhang

    (Chinese Center for Disease Control and Prevention
    Peking University First Hospital - National Institute for Communicable Disease Control and Prevention Joint Laboratory of Pathogenic Fungi)

  • Yuan-Yuan Geng

    (Chinese Center for Disease Control and Prevention
    Peking University First Hospital - National Institute for Communicable Disease Control and Prevention Joint Laboratory of Pathogenic Fungi)

  • 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
    Peking University First Hospital - National Institute for Communicable Disease Control and Prevention Joint Laboratory of Pathogenic Fungi)

  • Meng Xiao

    (Chinese Academy of Medical Sciences)

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.

Suggested Citation

  • 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 & Meng Xiao, 2023. "Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43380-2
    DOI: 10.1038/s41467-023-43380-2
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    References listed on IDEAS

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    2. Matthias Merker & Jean-Philippe Rasigade & Maxime Barbier & Helen Cox & Silke Feuerriegel & Thomas A. Kohl & Egor Shitikov & Kadri Klaos & Cyril Gaudin & Rudy Antoine & Roland Diel & Sonia Borrell & S, 2022. "Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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