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Nat Commun. 2016 Jul 22;7:12218. doi: 10.1038/ncomms12218.

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi.

Author information

1
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
2
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
3
Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
4
Fungal Reference Laboratory, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
5
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
6
David Geffen School of Medicine at UCLA, Los Angeles, California 90502, USA.
7
National Center for Agriculture Utilization Research, USDA, Agricultural Research Service, Peoria, Illinois 61604, USA.

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.

PMID:
27447865
PMCID:
PMC4961843
DOI:
10.1038/ncomms12218
[Indexed for MEDLINE]
Free PMC Article

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