Different toxicity mechanisms for citrinin and ochratoxin A revealed by transcriptomic analysis in yeast

The aim of this study was to reveal the genomic response of yeast cells to the related mycotoxins citrinin (CIT) and ochratoxin A (OTA). Both mycotoxins can be produced by the same filamentous fungi and co-contaminate the same foodstuff. However, it is not known whether CIT and OTA share the same toxicity mechanisms or not. We performed transcriptomic profiling experiments using microarray hybridization of a pdr5 mutant strain exposed separately to CIT or OTA and exposed to a combination of both toxins. A yeast pdr5 mutant was used, because it is significantly sensitized to both toxins. We find that CIT and OTA cause the rapid activation of largely non-overlapping gene sets. The most prominent functional group of CIT-activated genes corresponds to the cellular response to oxidative stress, while OTA-activated genes belong predominantly to single organism developmental processes and meiosis/sporulation. The combined exposure of CIT and OTA revealed a mixed response of functional gene groups. Our results demonstrate that CIT and OTA have distinguishable and independent biological effects with oxidative stress being a hallmark for CIT toxicity and the deregulation of developmental genes being the principal feature for OTA toxicity. Gene expression in yeast cells was measured under four conditions: control, citrinin (200ppm), ochratoxin A(200ppm), and a combination of both mycotoxins (100ppm of each). Samples were taken at 30 (ochratoxin A and combined treatment) and 60 min (control and citrinin). Four replicates were performed for each condition.