Exposure of Aspergillus fumigatus to T-2 toxin results in a stress response associated with exacerbation of aspergillosis in poultry

Abstract

Aspergillus fumigatus is a ubiquitous airborne pathogen. Saprophytic growth in the presence of environmental mycotoxins might affect its fitness and virulence. T-2 toxin (T-2) is a trichothecene mycotoxin produced by Fusarium spp. in various substrates. This study aimed to evaluate the effects of T-2 on the fitness of A. fumigatus in vitro and its virulence in experimentally inoculated chickens. We cultured A. fumigatus on agar media containing T-2, and examined the changes in viability, morphology, growth rate, proteome expression, and susceptibility to antimycotics and oxidative stress of this fungus. Results showed that exposure to 1000 ng/ml T-2 in the substrate did not reduce the viability of A. fumigatus, but its growth was inhibited, with wrinkling and depigmentation of the colonies. Proteomic analysis revealed 21 upregulated proteins and 33 downregulated proteins, including those involved in stress response, pathogenesis, metabolism, transcription. The proteome seems to have shifted to enhance the glycolysis, catabolism of lipids, and amino acid conversion. Assays on fungal susceptibility to antimycotics and oxidative stress showed that T-2 exposure did not affect the minimal inhibitory concentrations of amphotericin B, itraconazole, voriconazole and terbinafine against A. fumigatus, but increased the susceptibility of A. fumigatus to H2O2 and menadione. Experimental inoculation of chickens with A. fumigatus showed that exposure of A. fumigatus to T-2 significantly exacerbated aspergillosis in chickens exposed to dietary T-2. In conclusion, A. fumigatus is capable of surviving and growing on substrates containing levels of T-2 up to 1000 ng/ml. Growth in presence of T-2 induces a stress response in A. fumigatus, which is associated with exacerbation of aspergillosis in vivo.