Inheritance of resistance to fenpropimorph and terbinafine, two sterol biosynthesis inhibitors, in Nectria haematococca

The genetic control of resistance to two sterol biosynthesis inhibitors was investigated in the fungal pathogen Nectria haematococca. After UV light irradiation, resistant mutants were selected on either terbinafine, a squalene epoxidase inhibitor, or on fenpropimorph, an inhibitor of the sterol delta 14-reductase and/or delta 8 leads to delta 7-isomerase. They were genetically characterized by random analysis of sexually produced ascospores. In seven induced mutants, terbinafine resistance resulted from mutations in a single gene (Ter1), leading to high resistance levels. All these strains exhibited a positive cross-resistance towards other squalene epoxidase inhibitors (naftifine, tolnaftate). The genetic analysis of five fenpropimorph-resistant mutants resulted in the identification of three independent genes. The Fen1 gene was recognized in four mutants. One highly resistant mutant carried mutations in two unlinked genes, Fen2 and Fen3, which showed an important additive effect. Depending on the gene or on the allelic mutation involved, the fenpropimorph concentrations causing a 50% reduction in the mycelial growth rate ranged from 2.2 to 25.3 micrograms/ml. The corresponding values for the wild type strains were 0.1-0.2 micrograms/ml. Single gene mutants exhibited a positive cross-resistance towards fenpropidin but not always towards tridemorph. In most Ter1 mutants and in some Fen1 mutants, resistance was not coupled with changes in characteristics such as growth rate, sporulation, and pathogenicity. The potential risk of resistance development is discussed