title: An integrated genomic and transcriptomic survey of mucormycosis-causing fungi.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Marcus C
authors.identifier: http://orcid.org/0000-0001-9586-0780
authors.initials: MC
authors.lastname: Chibucos
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Sameh
authors.initials: S
authors.lastname: Soliman
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Teclegiorgis
authors.initials: T
authors.lastname: Gebremariam
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Hongkyu
authors.initials: H
authors.lastname: Lee
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Daugherty
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Orvis
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Amol C
authors.initials: AC
authors.lastname: Shetty
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crabtree
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Tracy H
authors.initials: TH
authors.lastname: Hazen
authors.affiliation: Fungal Reference Laboratory, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Kizee A
authors.initials: KA
authors.lastname: Etienne
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Kumari
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Connor
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.|David Geffen School of Medicine at UCLA, Los Angeles, California 90502, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.affiliation: Fungal Reference Laboratory, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.affiliation: National Center for Agriculture Utilization Research, USDA, Agricultural Research Service, Peoria, Illinois 61604, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Skory
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.|David Geffen School of Medicine at UCLA, Los Angeles, California 90502, USA.
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Bruno
mesh_terms: D000072283:A549 Cells; D000581:Amidohydrolases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005656:Fungal Proteins / Q000737:chemistry; D005800:Genes, Fungal; D016681:Genome, Fungal; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D058977:Molecular Sequence Annotation; D009090:Mucorales / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D009091:Mucormycosis / Q000382:microbiology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012233:Rhizopus / Q000235:genetics; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D059467:Transcriptome / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D000581:Amidohydrolases; C019866:chitin deacetylase