IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56269-z.html
   My bibliography  Save this article

Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata

Author

Listed:
  • Taiga Miyazaki

    (University of Miyazaki
    Nagasaki University Graduate School of Biomedical Sciences)

  • Shintaro Shimamura

    (Nagasaki University Graduate School of Biomedical Sciences
    St. Marianna University School of Medicine Hospital)

  • Yohsuke Nagayoshi

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Hironobu Nakayama

    (Suzuka University of Medical Sciences)

  • Akihiro Morita

    (Suzuka University of Medical Sciences)

  • Yutaka Tanaka

    (Tohoku Medical and Pharmaceutical University)

  • Yasuhiko Matsumoto

    (Meiji Pharmaceutical University)

  • Tatsuo Inamine

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Hiroshi Nishikawa

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Nana Nakada

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Makoto Sumiyoshi

    (University of Miyazaki)

  • Tatsuro Hirayama

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Shigeru Kohno

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Hiroshi Mukae

    (Nagasaki University Graduate School of Biomedical Sciences)

Abstract

Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C. glabrata cells to micafungin (an echinocandin) leads to the isolation of a mutant exhibiting resistance to echinocandin and azole antifungals. The drug-resistant phenotype is due to a non-synonymous mutation (R70H) in gene IPI1, which is involved in pre-rRNA processing. Azole resistance in the ipi1R70H mutant depends on the Pdr1 transcription factor, which regulates the expression of multidrug transporters. The C. glabrata Ipi1 protein physically interacts with the ribosome-related chaperones Ssb and Ssz1, both of which bind to Pdr1. The Ipi1-Ssb/Ssz1 complex inhibits Pdr1-mediated gene expression and multidrug resistance in C. glabrata, in contrast to Saccharomyces cerevisiae where Ssz1 acts as a positive regulator of Pdr1. Furthermore, micafungin exposure reduces metabolic activity and cell proliferation in the ipi1R70H mutant, which may contribute to micafungin tolerance.

Suggested Citation

  • Taiga Miyazaki & Shintaro Shimamura & Yohsuke Nagayoshi & Hironobu Nakayama & Akihiro Morita & Yutaka Tanaka & Yasuhiko Matsumoto & Tatsuo Inamine & Hiroshi Nishikawa & Nana Nakada & Makoto Sumiyoshi , 2025. "Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56269-z
    DOI: 10.1038/s41467-025-56269-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56269-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56269-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56269-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.