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Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance

Author

Listed:
  • Kelley R. Healey

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

  • Yanan Zhao

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

  • Winder B. Perez

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

  • Shawn R. Lockhart

    (Centers for Disease Control and Prevention)

  • Jack D. Sobel

    (Wayne State University School of Medicine)

  • Dimitrios Farmakiotis

    (The University of Texas MD Anderson Cancer Center
    Warren Alpert Medical School of Brown University)

  • Dimitrios P. Kontoyiannis

    (The University of Texas MD Anderson Cancer Center)

  • Dominique Sanglard

    (Institute of Microbiology of the University Hospital of Lausanne)

  • Saad J. Taj-Aldeen

    (Hamad Medical Corporation)

  • Barbara D. Alexander

    (Duke University)

  • Cristina Jimenez-Ortigosa

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

  • Erika Shor

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

  • David S. Perlin

    (Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences)

Abstract

The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy.

Suggested Citation

  • Kelley R. Healey & Yanan Zhao & Winder B. Perez & Shawn R. Lockhart & Jack D. Sobel & Dimitrios Farmakiotis & Dimitrios P. Kontoyiannis & Dominique Sanglard & Saad J. Taj-Aldeen & Barbara D. Alexander, 2016. "Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11128
    DOI: 10.1038/ncomms11128
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    Cited by:

    1. Wenping Zhu & Ying Li & Shaoxun Guo & Wu-Jie Guo & Tuokai Peng & Hui Li & Bin Liu & Hui-Qing Peng & Ben Zhong Tang, 2022. "Stereoisomeric engineering of aggregation-induced emission photosensitizers towards fungal killing," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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