A novel putative reductase (Cpd1p) and the multidrug exporter Snq2p are involved in resistance to cercosporin and other singlet oxygen-generating photosensitizers in Saccharomyces cerevisae

Phytopathogenic Cercospora species produce cercosporin, a photoactivated pe rylenequinone toxin that belongs to a family of photosensitizers which abso rb light energy and produce extremely cytotoxic, reactive oxygen species. I n this work, we used Saccharomyces cerevisiae as a model system for the ide ntification and cloning of genes whose products mediate cercosporin detoxif ication. Two genesexpressed in high-copy number vectors conferred cercospor in resistance to an otherwise sensitive strain. One gene codes for Snq2p, a well-characterized multidrug, ABC-type, efflux protein. The other, designa ted CPD1 (Cercosporin Photosensitizer Detoxification), encodes a novel prot ein with significant similarity to the FAD-dependent pyridine nucleotide re ductases. We showed that over-expression of either of these proteins can al so mediate resistance to other singlet oxygen-generating compounds. The inv olvement of Snq2p and Cpd1p in photosensitizer detoxification reinforces pr evious observations which suggested that singlet oxygen acts on membrane li pids and that cellular resistance to cercosporin is mediated by a mechanism involving toxin efflux and/or toxin reduction.