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

2020; Public Library of Science; Volume: 16; Issue: 7 Linguagem: Inglês

10.1371/journal.ppat.1008645

1553-7374

Laure Nicolas Annick Ries, Lakhansing Pardeshi, Zhiqiang Dong, Kaeling Tan, Jacob L. Steenwyk, Ana Cristina Colabardini, Jaire Alves Ferreira Filho, Patrícia Alves de Castro, Lilian Pereira Silva, Nycolas Willian Preite, Fausto Almeida, Leandro José de Assis, Renato Santos, Paul Bowyer, Michael Bromley, Rebecca A. Owens, Seán Doyle, Marilene Demasi, Diego Rodríguez‐Hernández, Luís Eduardo Soares Netto, Mônica Tallarico Pupo, Antonis Rokas, Flávio V. Loures, Koon Ho Wong, Gustavo H. Goldman,

Mycotoxins in Agriculture and Food

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.