Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance

BACKGROUND: The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis. OBJECTIVES: Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population. METHODS: Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay. RESULTS: Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance. CONCLUSION: The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.