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Effective treatment of systemic candidiasis by synergistic targeting of cell wall synthesis

Author

Listed:
  • Ju Yeon Chung

    (Korea Advanced Institute of Science and Technology)

  • Yoon-Kyoung Hong

    (University of Ulsan College of Medicine)

  • Eunhee Jeon

    (University of Ulsan College of Medicine)

  • Seungju Yang

    (Korea Advanced Institute of Science and Technology)

  • Ayoung Park

    (Korea Advanced Institute of Science and Technology)

  • Ralph Weissleder

    (Massachusetts General Brigham
    Harvard Medical School)

  • Yong Pil Chong

    (University of Ulsan College of Medicine)

  • Hyun Jung Chung

    (Korea Advanced Institute of Science and Technology)

Abstract

Fungal infections pose a serious threat to global human health fueled by the increase in immunosuppressive therapies, medical implants, and transplantation. The emergence of multidrug resistance with limited options of current antifungal drugs are a further constraint. There is thus a clear and unmet need to identify therapeutic targets and develop alternative classes of antifungal agents. Here, we hypothesize that dual targeting of key regulatory genes of fungal cell wall synthesis (FKS1 encoding β−1,3-glucan synthase and CHS3 encoding chitin synthase) can synergistically inhibit fungal growth. Based on iterative designs, we generate a small library of fungal-targeted nanoconstructs, and identify a lead construct (FTNx) that shows preferential accumulation in fungal cells over mammalian cells and leads to prominent antifungal effects in vitro. We further show that FTNx is highly effective in a mouse model of disseminated candidiasis, demonstrating diminished fungal growth and enhanced survival rate. This strategy appears promising as an effective treatment for fungal infections in mammalian hosts.

Suggested Citation

  • Ju Yeon Chung & Yoon-Kyoung Hong & Eunhee Jeon & Seungju Yang & Ayoung Park & Ralph Weissleder & Yong Pil Chong & Hyun Jung Chung, 2025. "Effective treatment of systemic candidiasis by synergistic targeting of cell wall synthesis," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60684-7
    DOI: 10.1038/s41467-025-60684-7
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    References listed on IDEAS

    as
    1. Matthew C. Fisher & Daniel. A. Henk & Cheryl J. Briggs & John S. Brownstein & Lawrence C. Madoff & Sarah L. McCraw & Sarah J. Gurr, 2012. "Emerging fungal threats to animal, plant and ecosystem health," Nature, Nature, vol. 484(7393), pages 186-194, April.
    2. Joy L. Nishikawa & Andras Boeszoermenyi & Luis A. Vale-Silva & Riccardo Torelli & Brunella Posteraro & Yoo-Jin Sohn & Fei Ji & Vladimir Gelev & Dominique Sanglard & Maurizio Sanguinetti & Ruslan I. Sa, 2016. "Inhibiting fungal multidrug resistance by disrupting an activator–Mediator interaction," Nature, Nature, vol. 530(7591), pages 485-489, February.
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