Role of sterol 3-ketoreductase sensitivity in susceptibility to the fungicide fenhexamid in Botrytis cinerea and other phytopathogenic fungi

BACKGROUND:Thenarrow-spectrumfungicidefenhexamidwasintroducedintoFrenchvineyardsin2000tocontrolgreymould caused by a complex of two cryptic species: Botrytis cinerea, the predominant species sensitive to fenhexamid, and Botrytis pseudocinerea, naturally resistant. Fenhexamid was suggested to inhibit the 3-ketoreductase involved at C-4 demethylation steps during ergosterol biosynthesis, as revealed by its effects on the B. cinerea sterol profile. Resistance monitoring studies have hitherto identified two B. cinerea fenhexamid-resistant phenotypes, both resulting from mutations in the erg27 gene encoding 3-ketoreductase. RESULTS: The role of 3-ketoreductase sensitivity in fungal susceptibility to fenhexamid was investigated by studying sterol profilesandmicrosomal3-ketoreductaseinvariousfungalstrains.FenhexamiddoesinhibitB.cinerea3-ketoreductaseactivity. Erg27 mutations causing amino acid substitutions in or near the transmembrane domain strongly decrease the affinity of fenhexamid for 3-ketoreductase. Fenhexamid has very low affinities for 3-ketoreductase in inherently resistant species, whether closely related to B.cinerea, like B.pseudocinerea, or more distantly related, like Nectriahaematococca. CONCLUSION: erg27 mutation and erg27 polymorphism may therefore contribute to the unfavourable binding of fenhexamid toitstarget,3-ketoreductase,explainingtheacquisitionoffenhexamidresistanceinB.cinereaandthenarrowspectrumofthis fungicide. c � 2012 Society of Chemical Industry Supporting information may be found in the online version of this article.