Oxidative stress response tips the balance in Aspergillus terreus AmB resistance [PublishAheadOfPrint]

In this study we characterize the impact of antioxidative enzymes in AmB resistant (ATR) and rare susceptible (ATS) clinical A. terreus isolates. We elucidate the expression profiles of superoxide dismutases (SODs) and catalases (CATs) encoding genes, enzymatic activity of SODs, superoxide anion production and signaling pathways involved in oxidative stress response (OSR) under AmB treatment in ATS and ATR strains. We show that ATR possess almost doubled basal SOD activity compared to ATS and that ATR exhibits an enhanced OSR, with significantly higher sod2 mRNA levels and significantly increased cat transcripts in ATR upon AmB treatment. In particular, inhibition of SOD- and CAT proteins rendered resistant isolates considerably susceptible to the drug in vitro. In conclusion, this study shows that Sods and Cats are crucial for AmB resistance in A. terreus and targeting the OSR might offer new treatment perspectives for resistant species.

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