An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

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 contr...

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Published in:Nature communications Vol. 7; no. 1; pp. 12218 - 11
Main Authors: Chibucos, Marcus C., Soliman, Sameh, Gebremariam, Teclegiorgis, Lee, Hongkyu, Daugherty, Sean, Orvis, Joshua, Shetty, Amol C., Crabtree, Jonathan, Hazen, Tracy H., Etienne, Kizee A., Kumari, Priti, O’Connor, Timothy D., Rasko, David A., Filler, Scott G., Fraser, Claire M., Lockhart, Shawn R., Skory, Christopher D., Ibrahim, Ashraf S., Bruno, Vincent M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 22.07.2016
Nature Publishing Group
Nature Portfolio
Subjects:
13/106
38/23
38/39
38/91
631/208/325/2484
631/326/193/2540
692/699/255/1672
96/95
A549 Cells
Amidohydrolases - metabolism
Amino Acid Sequence
Animals
Annotations
Base Sequence
Comparative analysis
Debridement
Disease
Economic importance
Fungal Proteins - chemistry
Fungi
Genes, Fungal
Genome, Fungal
Genomes
Humanities and Social Sciences
Humans
Infections
Male
Medicine
Mice, Inbred ICR
Molecular Sequence Annotation
Mortality
Mucorales - enzymology
Mucorales - genetics
Mucorales - isolation & purification
Mucormycosis - microbiology
multidisciplinary
Neutropenia
Pathogenesis
Phylogenetics
Phylogeny
Polymorphism, Single Nucleotide - genetics
Rhizopus - genetics
Science
Science (multidisciplinary)
Sequence Analysis, RNA
Species Specificity
Transcriptome - genetics
Los Angeles California
California
United States > US
Maryland
Baltimore Maryland
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Fungi of the order Mucorales can cause life-threatening infections. Here, Chibucos et al . present genomic and transcriptomic analyses of a diverse set of Mucorales fungi, shedding light on their evolution and identifying potential therapeutic targets in the pathogens and the host.
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Present address: Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, UAE.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms12218