Cross-resistance to strobilurin fungicides in mitochondrial and nuclear mutants of Saccharomyces cerevisiae.

In yeast the resistance to kresoxim-methyl and azoxystrobin, like the resistance to strobilurin A (mucidin) is under the control of both mitochondrialcob gene and the PDR network of nuclear genes involved in multidrug resistance. The mucidin-resistantmucl (G137R) andmuc2 (L275S) mutants ofSaccharomyces cerevisiae containing point mutations in mtDNA were found to be cross-resistant to kresoximmethyl and azoxystrobin. Cross-resistance to all three strobilurin fungicides was also observed in yeast transformants containing gain-of-function mutations in the nuclearPDR3 gene. On the other hand, nuclear mutants containing disrupted chromosomal copies of thePDR1 andPDR3 genes or thePDR5 gene alone werehypersensitive to kresoxim-methyl, axoxystrobin 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 apocytochromeb and/or increased efflux of strobilurins from fungal cells.