Components of a new gene family of ferroxidases involved in virulence are functionally specialized in fungal dimorphism

Scientific Reports
María Isabel Navarro-MendozaVictoriano Garre

Abstract

Mucormycosis is an emerging angio-invasive infection caused by Mucorales that presents unacceptable mortality rates. Iron uptake has been related to mucormycosis, since serum iron availability predisposes the host to suffer this infection. In addition, iron uptake has been described as a limiting factor that determines virulence in other fungal infections, becoming a promising field to study virulence in Mucorales. Here, we identified a gene family of three ferroxidases in Mucor circinelloides, fet3a, fet3b and fet3c, which are overexpressed during infection in a mouse model for mucormycosis, and their expression in vitro is regulated by the availability of iron in the culture media and the dimorphic state. Thus, only fet3a is specifically expressed during yeast growth under anaerobic conditions, whereas fet3b and fet3c are specifically expressed in mycelium during aerobic growth. A deep genetic analysis revealed partially redundant roles of the three genes, showing a predominant role of fet3c, which is required for virulence during in vivo infections, and shared functional roles with fet3b and fet3c during vegetative growth in media with low iron concentration. These results represent the first described functional specializat...Continue Reading

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Mar 1, 2019·Medical Mycology·Mohamed I Abdelwahab Hassan, Kerstin Voigt
Feb 11, 2020·BMC Genomics·Annie LebretonLaurence Meslet-Cladière
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Methods Mentioned

BETA
reverse transcription quantitative PCR
PCR
dissection

Software Mentioned

Gblocks
ImageJ
PhyML
BLAST
GraphPad
MUSCLE
Graph Pad Prism

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