Insights into yeast adaptive response to the agricultural fungicide mancozeb: A toxicoproteomics approach

Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans.