Nature Communications (Dec 2020)
An oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida auris
- Kali R. Iyer,
- Kaddy Camara,
- Martin Daniel-Ivad,
- Richard Trilles,
- Sheila M. Pimentel-Elardo,
- Jen L. Fossen,
- Karen Marchillo,
- Zhongle Liu,
- Shakti Singh,
- José F. Muñoz,
- Sang Hu Kim,
- John A. Porco,
- Christina A. Cuomo,
- Noelle S. Williams,
- Ashraf S. Ibrahim,
- John E. Edwards,
- David R. Andes,
- Justin R. Nodwell,
- Lauren E. Brown,
- Luke Whitesell,
- Nicole Robbins,
- Leah E. Cowen
Affiliations
- Kali R. Iyer
- Department of Molecular Genetics, University of Toronto
- Kaddy Camara
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Martin Daniel-Ivad
- Department of Biochemistry, University of Toronto
- Richard Trilles
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Sheila M. Pimentel-Elardo
- Department of Biochemistry, University of Toronto
- Jen L. Fossen
- Department of Medicine, University of Wisconsin School of Medicine and Public Health
- Karen Marchillo
- Department of Medicine, University of Wisconsin School of Medicine and Public Health
- Zhongle Liu
- Department of Molecular Genetics, University of Toronto
- Shakti Singh
- Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles (UCLA) Medical Center
- José F. Muñoz
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard
- Sang Hu Kim
- Department of Molecular Genetics, University of Toronto
- John A. Porco
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Christina A. Cuomo
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard
- Noelle S. Williams
- Department of Biochemistry, University of Texas Southwestern Medical School
- Ashraf S. Ibrahim
- Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles (UCLA) Medical Center
- John E. Edwards
- Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles (UCLA) Medical Center
- David R. Andes
- Department of Medicine, University of Wisconsin School of Medicine and Public Health
- Justin R. Nodwell
- Department of Biochemistry, University of Toronto
- Lauren E. Brown
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Luke Whitesell
- Department of Molecular Genetics, University of Toronto
- Nicole Robbins
- Department of Molecular Genetics, University of Toronto
- Leah E. Cowen
- Department of Molecular Genetics, University of Toronto
- DOI
- https://doi.org/10.1038/s41467-020-20183-3
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 17
Abstract
The fungal pathogen Candida auris is resistant to multiple drugs including the common antifungal fluconazole. Here, Iyer et al. identify a compound that potentiates fluconazole activity against C. auris in vitro and in vivo by inhibiting a major efflux pump and thus increasing intracellular fluconazole accumulation.
