The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

PLoS Pathogens
Laure N A RiesGustavo H Goldman

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-media...Continue Reading

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Citations

Mar 7, 2021·Journal of Fungi·Yidong YuAndreas Beilhack
Jul 20, 2021·Reports of Biochemistry & Molecular Biology·Bahareh ArghavanSassan Rezaie

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Datasets Mentioned

BETA
SRP154617
PRJNA574873

Methods Mentioned

BETA
protein folding
RNA-seq
immunoprecipitation
ChIP-seq
ChIPseq

Software Mentioned

R
MEME EM for
Tree
trimAl
MEME
tximport
DiffBind
MACS2
Caper
Blast +

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