An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  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.
• Description:
  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.
• Subjects:
  A549 Cells Amidohydrolases Amino Acid Sequence Animals Base Sequence Fungal Proteins Genes, Fungal Genome, Fungal Humans Male Mice, Inbred ICR Molecular Sequence Annotation Mucorales Mucormycosis Phylogeny Polymorphism, Single Nucleotide Rhizopus Sequence Analysis, RNA Species Specificity Transcriptome

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• Source:
  Nat Commun. 2016; 7.
• Pubmed ID:
  27447865
• Pubmed Central ID:
  PMC4961843
• Document Type:
  Journal Article
• Volume:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0dd0d0b4d629446197985811c3b73795378ada07c21bc943d119f20d6c41b168
• Download URL:
  https://stacks.cdc.gov/view/cdc/41506/cdc_41506_DS1.pdf
• File Type:
  [PDF - 1.31 MB ]