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

BACKGROUND The Indian ITS genotype VIII T. mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyzes 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 analyzed 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.