Ries, Laure Nocolas Annick and Pardeshi, Lakhansing and Dong, Zhiqiang and Tan, Kaeling and Steenwyk, Jacob L and Colabardini, Ana Christina and Ferreira Filho, Jaire A. and de Castro, Patricia A. and Silva, Lilian Pereira and Preite, Nycolas W and Almeida, Fausto and de Assis, Leandro J and dos Santos, Renato A C and Bowyer, Paul and Bromley, Michael and Owens, Rebecca A. and Doyle, Sean and Demasi, Marilene and Hernandez, Diego C R and Netto, Luis Eduardo S and Pupo, Monica T and Rokas, Antonis and Loures, Flavio V and Wong, Koon H and Goldman, Gustavo H (2020) The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS Pathogens, 16 (7). e1008645. ISSN 1553-7366

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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-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.

Item Type:	Article
Keywords:	Aspergillus fumigatus; transcription; factor RglT; gliotoxin biosynthesis; self-protection; virulence;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	14969
Identification Number:	https://doi.org/10.1371/journal.ppat.1008645
Depositing User:	Rebecca Owens
Date Deposited:	01 Nov 2021 16:17
Journal or Publication Title:	PLOS Pathogens
Publisher:	Public Library of Science
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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