title: Cross-resistance to strobilurin fungicides in mitochondrial and nuclear mutants of Saccharomyces cerevisiae.
abstract: In yeast the resistance to kresoxim-methyl and azoxystrobin, like the resistance to strobilurin A (mucidin) is under the control of both mitochondrial cob gene and the PDR network of nuclear genes involved in multidrug resistance. The mucidin-resistant mucl (G137R) and muc2 (L275S) mutants of Saccharomyces cerevisiae containing point mutations in mtDNA were found to be cross-resistant to kresoxim-methyl and azoxystrobin. Cross-resistance to all three strobilurin fungicides was also observed in yeast transformants containing gain-of-function mutations in the nuclear PDR3 gene. On the other hand, nuclear mutants containing disrupted chromosomal copies of the PDR1 and PDR3 genes or the PDR5 gene alone were hypersensitive to kresoxim-methyl, azoxystrobin and strobilurin A. The frequencies of spontaneous mutants selected for resistance either to kresoxim-methyl, azoxystrobin or strobilurin A were similar and resulted from mutations both in mitochondrial and nuclear genes. The results indicate that resistance to strobilurin fungicides, differing in chemical structure and specific activity, can be caused by the same molecular mechanism involving changes in the structure of apocytochrome b and/or increased efflux of strobilurins from fungal cells.
authors.affiliation: Department of Microbiology and Virology, Faculty of Science, Comenius University, 842 15 Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Hnátová
authors.forename: Y
authors.initials: Y
authors.lastname: Gbelská
authors.forename: M
authors.initials: M
authors.lastname: Obernauerová
authors.forename: V
authors.initials: V
authors.lastname: Subíková
authors.forename: J
authors.initials: J
authors.lastname: Subík
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000179:Acrylates / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D005659:Fungicides, Industrial / Q000494:pharmacology; D005800:Genes, Fungal; D008689:Methacrylates; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000235:genetics; D009154:Mutation; D010648:Phenylacetates / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D000073739:Strobilurins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000179:Acrylates; D000935:Antifungal Agents; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D008689:Methacrylates; C085480:PDR1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D010648:Phenylacetates; D011743:Pyrimidines; D029701:Saccharomyces cerevisiae Proteins; D000073739:Strobilurins; D015534:Trans-Activators; D014157:Transcription Factors; C469328:kresoxim-methyl; C008556:mucidin; C087670:azoxystrobin