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An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

Author

Listed:
  • Marcus C. Chibucos

    (University of Maryland School of Medicine
    Institute for Genome Sciences, University of Maryland School of Medicine)

  • Sameh Soliman

    (Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
    Present address: Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, UAE.)

  • Teclegiorgis Gebremariam

    (Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center)

  • Hongkyu Lee

    (Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center)

  • Sean Daugherty

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Joshua Orvis

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Amol C. Shetty

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Jonathan Crabtree

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Tracy H. Hazen

    (University of Maryland School of Medicine
    Institute for Genome Sciences, University of Maryland School of Medicine)

  • Kizee A. Etienne

    (Fungal Reference Laboratory, Mycotic Diseases Branch, Centers for Disease Control and Prevention)

  • Priti Kumari

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Timothy D. O’Connor

    (Institute for Genome Sciences, University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • David A. Rasko

    (University of Maryland School of Medicine
    Institute for Genome Sciences, University of Maryland School of Medicine)

  • Scott G. Filler

    (Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
    David Geffen School of Medicine at UCLA)

  • Claire M. Fraser

    (Institute for Genome Sciences, University of Maryland School of Medicine)

  • Shawn R. Lockhart

    (Fungal Reference Laboratory, Mycotic Diseases Branch, Centers for Disease Control and Prevention)

  • Christopher D. Skory

    (National Center for Agriculture Utilization Research, USDA, Agricultural Research Service)

  • Ashraf S. Ibrahim

    (Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
    David Geffen School of Medicine at UCLA)

  • Vincent M. Bruno

    (University of Maryland School of Medicine
    Institute for Genome Sciences, University of Maryland School of Medicine)

Abstract

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets.

Suggested Citation

  • Marcus C. Chibucos & Sameh Soliman & Teclegiorgis Gebremariam & Hongkyu Lee & Sean Daugherty & Joshua Orvis & Amol C. Shetty & Jonathan Crabtree & Tracy H. Hazen & Kizee A. Etienne & Priti Kumari & Ti, 2016. "An integrated genomic and transcriptomic survey of mucormycosis-causing fungi," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12218
    DOI: 10.1038/ncomms12218
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    Cited by:

    1. Povilas Kavaliauskas & Yiyou Gu & Naushaba Hasin & Karen T. Graf & Abdullah Alqarihi & Amol C. Shetty & Carrie McCracken & Thomas J. Walsh & Ashraf S. Ibrahim & Vincent M. Bruno, 2024. "Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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