IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38220-2.html
   My bibliography  Save this article

A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi

Author

Listed:
  • Liqing Hu

    (Virginia Commonwealth University
    Central South University
    Hunan Normal University)

  • Cancan Sun

    (Virginia Commonwealth University)

  • Justin M. Kidd

    (Virginia Commonwealth University)

  • Jizhong Han

    (Shenzhen Bay Laboratory)

  • Xianjun Fang

    (Virginia Commonwealth University)

  • Hongtao Li

    (Virginia Commonwealth University)

  • Qingdai Liu

    (Tianjin University of Science & Technology)

  • Aaron E. May

    (Virginia Commonwealth University)

  • Qianbin Li

    (Central South University)

  • Lei Zhou

    (Shenzhen Bay Laboratory)

  • Qinglian Liu

    (Virginia Commonwealth University)

Abstract

Proteins of the Hsp110 family are molecular chaperones that play important roles in protein homeostasis in eukaryotes. The pathogenic fungus Candida albicans, which causes infections in humans, has a single Hsp110, termed Msi3. Here, we provide proof-of-principle evidence supporting fungal Hsp110s as targets for the development of new antifungal drugs. We identify a pyrazolo[3,4-b] pyridine derivative, termed HLQ2H (or 2H), that inhibits the biochemical and chaperone activities of Msi3, as well as the growth and viability of C. albicans. Moreover, the fungicidal activity of 2H correlates with its inhibition of in vivo protein folding. We propose 2H and related compounds as promising leads for development of new antifungals and as pharmacological tools for the study of the molecular mechanisms and functions of Hsp110s.

Suggested Citation

  • Liqing Hu & Cancan Sun & Justin M. Kidd & Jizhong Han & Xianjun Fang & Hongtao Li & Qingdai Liu & Aaron E. May & Qianbin Li & Lei Zhou & Qinglian Liu, 2023. "A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38220-2
    DOI: 10.1038/s41467-023-38220-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38220-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38220-2?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
    ---><---

    References listed on IDEAS

    as
    1. Alexander Rosenberg & Iuliana V. Ene & Maayan Bibi & Shiri Zakin & Ella Shtifman Segal & Naomi Ziv & Alon M. Dahan & Arnaldo Lopes Colombo & Richard J. Bennett & Judith Berman, 2018. "Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Vasant Muralidharan & Anna Oksman & Priya Pal & Susan Lindquist & Daniel E. Goldberg, 2012. "Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    3. Luke Whitesell & Nicole Robbins & David S. Huang & Catherine A. McLellan & Tanvi Shekhar-Guturja & Emmanuelle V. LeBlanc & Catherine S. Nation & Raymond Hui & Ashley Hutchinson & Cathy Collins & Shara, 2019. "Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gerry Q Tonkin-Hill & Leily Trianty & Rintis Noviyanti & Hanh H T Nguyen & Boni F Sebayang & Daniel A Lampah & Jutta Marfurt & Simon A Cobbold & Janavi S Rambhatla & Malcolm J McConville & Stephen J R, 2018. "The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes," PLOS Biology, Public Library of Science, vol. 16(3), pages 1-40, March.
    2. Amir Arastehfar & Farnaz Daneshnia & Nathaly Cabrera & Suyapa Penalva-Lopez & Jansy Sarathy & Matthew Zimmerman & Erika Shor & David S. Perlin, 2023. "Macrophage internalization creates a multidrug-tolerant fungal persister reservoir and facilitates the emergence of drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Neil A. R. Gow & Carolyn Johnson & Judith Berman & Alix T. Coste & Christina A. Cuomo & David S. Perlin & Tihana Bicanic & Thomas S. Harrison & Nathan Wiederhold & Mike Bromley & Tom Chiller & Keegan , 2022. "The importance of antimicrobial resistance in medical mycology," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    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:14:y:2023:i:1:d:10.1038_s41467-023-38220-2. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.