An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

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, Timothy D. O’Connor, David A. Rasko, Scott G. Filler, Claire M. Fraser, Shawn R. Lockhart, Christopher D. Skory, Ashraf S. Ibrahim () and Vincent M. Bruno ()
Additional contact information
Marcus C. Chibucos: University of Maryland School of Medicine
Sameh Soliman: Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
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
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
David A. Rasko: University of Maryland School of Medicine
Scott G. Filler: Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
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
Vincent M. Bruno: University of Maryland School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12218

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