IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60991-z.html
   My bibliography  Save this article

Colistin enhances caspofungin antifungal efficacy against Aspergillus fumigatus by modulating calcium homeostasis and stress responses

Author

Listed:
  • Laura Garcia Carnero

    (Universidade de São Paulo)

  • Xingyue Li

    (Nanjing Normal University)

  • Patrícia Alves de Castro

    (Universidade de São Paulo)

  • Camila Figueiredo Pinzan

    (Universidade de São Paulo)

  • Jonatas Erick Maimoni Campanella

    (Universidade Federal de São Carlos)

  • Iran Malavazi

    (Universidade Federal de São Carlos
    National Institute of Science and Technology in Human Pathogenic Fungi)

  • Mami Yoshimura

    (RIKEN Center for Sustainable Resource Science)

  • Luis Alberto Vega Isuhuaylas

    (University of Toronto)

  • Yoko Yashiroda

    (RIKEN Center for Sustainable Resource Science)

  • Charles Boone

    (RIKEN Center for Sustainable Resource Science
    University of Toronto
    University of Toronto)

  • Nir Osherov

    (Tel-Aviv University)

  • Sara Fallah

    (University of Toronto)

  • Taylor Davie

    (University of Toronto)

  • Nicole Robbins

    (University of Toronto)

  • Leah Cowen

    (University of Toronto)

  • Ling Lu

    (Nanjing Normal University)

  • Thaila Fernanda dos Reis

    (Universidade de São Paulo
    National Institute of Science and Technology in Human Pathogenic Fungi)

  • Gustavo H. Goldman

    (Universidade de São Paulo
    National Institute of Science and Technology in Human Pathogenic Fungi)

Abstract

Fungal infections cause more than 2.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, by screening a collection of 5297 compounds derived from three chemical libraries, we demonstrate that the antibacterial agent colistin (COL) can potentiate the fungistatic echinocandins caspofungin (CAS) and anidulafungin, as well as the structurally distinct cell wall targeting antifungal ibrexafungerp against Aspergillus fumigatus. Chemical and genetic screenings revealed that protein kinase C and the transcription factor SltA are involved in the mechanism of action of COL. SltA is essential for coping with calcium-limiting conditions, and the addition of calcium rescues COL-susceptibility. COL + CAS decreases A. fumigatus infection in human pulmonary cells, Galleria mellonella, and Caenorhabditis elegans. In summary, we demonstrate that the mechanism of COL as a synergizer of CAS against A. fumigatus is the disruption of the cell membrane permeability and calcium homeostasis.

Suggested Citation

  • Laura Garcia Carnero & Xingyue Li & Patrícia Alves de Castro & Camila Figueiredo Pinzan & Jonatas Erick Maimoni Campanella & Iran Malavazi & Mami Yoshimura & Luis Alberto Vega Isuhuaylas & Yoko Yashir, 2025. "Colistin enhances caspofungin antifungal efficacy against Aspergillus fumigatus by modulating calcium homeostasis and stress responses," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60991-z
    DOI: 10.1038/s41467-025-60991-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60991-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60991-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
    ---><---

    References listed on IDEAS

    as
    1. Michael J. Bottery & Norman Rhijn & Harry Chown & Johanna L. Rhodes & Brandi N. Celia-Sanchez & Marin T. Brewer & Michelle Momany & Matthew C. Fisher & Christopher G. Knight & Michael J. Bromley, 2024. "Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Takanori Furukawa & Norman van Rhijn & Marcin Fraczek & Fabio Gsaller & Emma Davies & Paul Carr & Sara Gago & Rachael Fortune-Grant & Sayema Rahman & Jane Mabey Gilsenan & Emma Houlder & Caitlin H. Ko, 2020. "The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. Norman Rhijn & Can Zhao & Narjes Al-Furaiji & Isabelle S. R. Storer & Clara Valero & Sara Gago & Harry Chown & Clara Baldin & Rachael-Fortune Grant & Hajer Shuraym & Lia Ivanova & Olaf Kniemeyer & Tho, 2024. "Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Norman Rhijn & Can Zhao & Narjes Al-Furaiji & Isabelle S. R. Storer & Clara Valero & Sara Gago & Harry Chown & Clara Baldin & Rachael-Fortune Grant & Hajer Shuraym & Lia Ivanova & Olaf Kniemeyer & Tho, 2024. "Author Correction: Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging," Nature Communications, Nature, vol. 15(1), pages 1-1, December.
    5. Dante G. Calise & Sung Chul Park & Jin Woo Bok & Gustavo H. Goldman & Nancy P. Keller, 2024. "An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Nicola Nosengo, 2016. "Can you teach old drugs new tricks?," Nature, Nature, vol. 534(7607), pages 314-316, June.
    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. Jinhong Xie & Jeffrey M. Rybak & Adela Martin-Vicente & Xabier Guruceaga & Harrison I. Thorn & Ashley V. Nywening & Wenbo Ge & Josie E. Parker & Steven L. Kelly & P. David Rogers & Jarrod R. Fortwende, 2024. "The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Norman Rhijn & Can Zhao & Narjes Al-Furaiji & Isabelle S. R. Storer & Clara Valero & Sara Gago & Harry Chown & Clara Baldin & Rachael-Fortune Grant & Hajer Shuraym & Lia Ivanova & Olaf Kniemeyer & Tho, 2024. "Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Shin, Hyunjin & Woo, Hyun Goo & Sohn, Kyung-Ah & Lee, Sungjoo, 2023. "Comparing research trends with patenting activities in the biomedical sector: The case of dementia," Technological Forecasting and Social Change, Elsevier, vol. 195(C).
    4. Kouichi Hosomi & Mai Fujimoto & Kazutaka Ushio & Lili Mao & Juran Kato & Mitsutaka Takada, 2018. "An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-19, October.
    5. Michael J. Bottery & Norman Rhijn & Harry Chown & Johanna L. Rhodes & Brandi N. Celia-Sanchez & Marin T. Brewer & Michelle Momany & Matthew C. Fisher & Christopher G. Knight & Michael J. Bromley, 2024. "Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Stefan Wolf & Matiar Madanchi & Patrick Turko & Maija Hollmén & Sonia Tugues & Julia Atzigen & Pietro Giovanoli & Reinhard Dummer & Nicole Lindenblatt & Cornelia Halin & Michael Detmar & Mitchell Leve, 2024. "Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3+ Treg population," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Paul Bowyer & Andrew Currin & Daniela Delneri & Marcin G. Fraczek, 2022. "Telomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    8. Peter C. Cook & Sheila L. Brown & Emma L. Houlder & Julio Furlong-Silva & Daniel P. Conn & Stefano A. P. Colombo & Syed Baker & Freya R. Svedberg & Gareth Howell & Margherita Bertuzzi & Louis Boon & J, 2025. "Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    9. Thaila Fernanda Reis & Patrícia Alves Castro & Rafael Wesley Bastos & Camila Figueiredo Pinzan & Pedro F. N. Souza & Suzanne Ackloo & Mohammad Anwar Hossain & David Harold Drewry & Sondus Alkhazraji &, 2023. "A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. 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.
    11. Arnab Chakraborty & Liyanage D. Fernando & Wenxia Fang & Malitha C. Dickwella Widanage & Pingzhen Wei & Cheng Jin & Thierry Fontaine & Jean-Paul Latgé & Tuo Wang, 2021. "A molecular vision of fungal cell wall organization by functional genomics and solid-state NMR," Nature Communications, Nature, vol. 12(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:16:y:2025:i:1:d:10.1038_s41467-025-60991-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.

    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.