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

Pest Manag Sci. 2013 May;69(5):642-51. doi: 10.1002/ps.3418. Epub 2012 Nov 9.

Abstract

Background: The narrow-spectrum fungicide fenhexamid was introduced into French vineyards in 2000 to control grey mould 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 profiles and microsomal 3-ketoreductase in various fungal strains. Fenhexamid does inhibit B. cinerea 3-ketoreductase activity. 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 Nectria haematococca.

Conclusion: erg27 mutation and erg27 polymorphism may therefore contribute to the unfavourable binding of fenhexamid to its target, 3-ketoreductase, explaining the acquisition of fenhexamid resistance in B. cinerea and the narrow spectrum of this fungicide.

MeSH terms

  • Amides / chemistry*
  • Botrytis / chemistry
  • Botrytis / enzymology*
  • Botrytis / genetics
  • Drug Resistance, Fungal / genetics*
  • Ergosterol / biosynthesis
  • Fungal Proteins / antagonists & inhibitors*
  • Mutation
  • Plant Diseases / microbiology
  • Polymorphism, Genetic

Substances

  • Amides
  • Fungal Proteins
  • N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide
  • Ergosterol