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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961843/
https://www.ncbi.nlm.nih.gov/pubmed/27447865
http://dx.doi.org/10.1038/ncomms12218
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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.
author_facet 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.
author_sort Chibucos, Marcus C.
collection PubMed
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.
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spelling pubmed-49618432016-09-06 An integrated genomic and transcriptomic survey of mucormycosis-causing fungi 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. Nat Commun Article 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. Nature Publishing Group 2016-07-22 /pmc/articles/PMC4961843/ /pubmed/27447865 http://dx.doi.org/10.1038/ncomms12218 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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.
An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title_full An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title_fullStr An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title_full_unstemmed An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title_short An integrated genomic and transcriptomic survey of mucormycosis-causing fungi
title_sort integrated genomic and transcriptomic survey of mucormycosis-causing fungi
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961843/
https://www.ncbi.nlm.nih.gov/pubmed/27447865
http://dx.doi.org/10.1038/ncomms12218
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