Cross-Resistance Relationships between Zoxamide, Carbendazim and Diethofencarb in Field Isolates ofBotrytis cinerea and other Fungi

摘要

The antitubulin benzamide fungicide zoxamide was introduced commercially to control Oomycete diseases 4 years ago. Since its commercial introduction, there have been no reports of reduced sensitivity in field isolates, and attempts to isolate benzamide-resistant mutants in Oomycetes in the laboratory have not been successful. This differs from previous experience with benzimidazole fungicides such as carbendazim and the N-phenylcarbamate diethofencarb which also act on tubulin. These materials rapidly encountered high levels of field resistance shortly after then- introduction due to specific mutations in p-tubulin. Zoxamide differs structurally from the benzimidazoles and diethofencarb, and exhibits the unusual property among antitubulin agents ofcovalent binding to tubulin. In terms of its potential for resistance development in a commercial setting the most significant feature which differentiates zoxamide from benziniidazoles and diethofencarb is the diploid nature of its Oomycete target organisms. Tubulin mutations which might affect binding of zoxamide are likely to be recessive, therefore a heterozygous diploid harboring such a mutation should still be sensitive to zoxamide. Although zoxamide only displays commercial-level efficacy againstOomycetes it shows a lower level of fungitoxicity against other fungi in culture. As one approach to explore the binding site for zoxamide on p-tubulin, we have evaluated fungal isolates which show resistance to benzimidazoles and diethofencarb for sensitivity to zoxamide and another benzamide, RH-1716. Benzimidazole-resistant strains ofBotrytis cinerea, Venturia inaequalis, Monilinia fructicola and Cercospora beticola, which are sensitive to diethofencarb due to negatively-correlated cross-resistance,were found to show enhanced sensitivity to the' benzamides. rn contrast, strains of B. cinerea and V. inaequalis which are resistant to both carbendazim and diethofencarb were found to be cross-resistant to the benzamides. These results suggest that zoxamide, carbendazim and diethofencarb bind to the same general region on P-tubulin. However, the insensitivity of Oomycetes to benzimidazoles and diethofencarb and much higher sensitivity to benzamides point to significant structural differences in this region between Oomycetes and other fungi.