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Inhibiting fungal multidrug resistance by disrupting an activator–Mediator interaction

Author

Listed:
  • Joy L. Nishikawa

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Andras Boeszoermenyi

    (Harvard Medical School)

  • Luis A. Vale-Silva

    (Institute of Microbiology, University Hospital Lausanne and University Hospital Center)

  • Riccardo Torelli

    (Institute of Microbiology, Università Cattolica del Sacro Cuore)

  • Brunella Posteraro

    (Institute of Public Health, Università Cattolica del Sacro Cuore)

  • Yoo-Jin Sohn

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Fei Ji

    (Massachusetts General Hospital, Boston
    Harvard Medical School)

  • Vladimir Gelev

    (Faculty of Chemistry and Pharmacy, Sofia University)

  • Dominique Sanglard

    (Institute of Microbiology, University Hospital Lausanne and University Hospital Center)

  • Maurizio Sanguinetti

    (Institute of Microbiology, Università Cattolica del Sacro Cuore)

  • Ruslan I. Sadreyev

    (Massachusetts General Hospital, Boston
    Massachusetts General Hospital and Harvard Medical School)

  • Goutam Mukherjee

    (Indian Institute of Technology Delhi
    Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology Delhi)

  • Jayaram Bhyravabhotla

    (Indian Institute of Technology Delhi
    Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology Delhi
    Kusuma School of Biological Sciences, Indian Institute of Technology Delhi)

  • Sara J. Buhrlage

    (Harvard Medical School
    Dana-Farber Cancer Institute)

  • Nathanael S. Gray

    (Harvard Medical School
    Dana-Farber Cancer Institute)

  • Gerhard Wagner

    (Harvard Medical School)

  • Anders M. Näär

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Haribabu Arthanari

    (Harvard Medical School)

Abstract

A small molecule, inhibitor of a protein–protein interaction between the transcription factor Pdr1 and the Med15 subunit of Mediator in the fungal pathogen Candida glabrata, is identified and characterized here; the compound iKIX1 inhibits Pdr1-mediated gene activation and resensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models of disseminated and urinary tract infection.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:nature:v:530:y:2016:i:7591:d:10.1038_nature16963
    DOI: 10.1038/nature16963
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    Cited by:

    1. Vladislav N. Nikolov & Dhara Malavia & Takashi Kubota, 2022. "SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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