An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

被引：104

作者：

Chibucos, Marcus C. ^{[1
,2
]}

Soliman, Sameh ^{[3
,8
]}

Gebremariam, Teclegiorgis ^{[3
]}

Lee, Hongkyu ^{[3
]}

Daugherty, Sean ^{[2
]}

Orvis, Joshua ^{[2
]}

Shetty, Amol C. ^{[2
]}

Crabtree, Jonathan ^{[2
]}

Hazen, Tracy H. ^{[1
,2
]}

Etienne, Kizee A. ^{[4
]}

Kumari, Priti ^{[2
]}

O'Connor, Timothy D. ^{[2
,5
]}

Rasko, David A. ^{[1
,2
]}

Filler, Scott G. ^{[3
,6
]}

Fraser, Claire M. ^{[2
]}

Lockhart, Shawn R. ^{[4
]}

Skory, Christopher D. ^{[7
]}

Ibrahim, Ashraf S. ^{[3
,6
]}

Bruno, Vincent M. ^{[1
,2
]}

机构：

[1] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA

[3] Harbor UCLA Med Ctr, Div Infect Dis, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA

[4] Ctr Dis Control & Prevent, Fungal Reference Lab, Mycot Dis Branch, Atlanta, GA 30333 USA

[5] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90502 USA

[7] ARS, Natl Ctr Agr Utilizat Res, USDA, Peoria, IL 61604 USA

[8] Univ Sharjah, Dept Med Chem, Coll Pharm, POB 27272, Sharjah, U Arab Emirates

来源：

Nature Communications | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

MAXIMUM-LIKELIHOOD PHYLOGENIES; CANDIDA-ALBICANS INFECTION; RHIZOPUS-ORYZAE; PROINFLAMMATORY RESPONSE; TRANSPLANT RECIPIENTS; SEQUENCE ALIGNMENTS; ENDOTHELIAL-CELLS; ZYGOMYCOSIS; PHOSPHORYLATION; EPIDEMIOLOGY;

D O I：

10.1038/ncomms12218

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 75 条

[1] Rhizopus delemar is the proper name for Rhizopus oryzae fumaric-malic acid producers [J].