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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Ries LNA,Pardeshi L,Dong Z,Tan K,Steenwyk JL,Colabardini AC,Ferreira Filho JA,de Castro PA,Silva LP,Preite NW,Almeida F,de Assis LJ,Dos Santos RAC,Bowyer P,Bromley M,Owens RA,Doyle S,Demasi M,Hernández DCR,Netto LESdoi
10.1371/journal.ppat.1008645subject
Has Abstractpub_date
2020-07-15 00:00:00pages
e1008645issue
7eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-20-00609journal_volume
16pub_type
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