Antifungal Susceptibility and Mutations in the Squalene Epoxidase Gene in Dermatophytes of the Trichophyton mentagrophytes Species Complex.

During the past decade, a prolonged and serious outbreak of dermatophytosis due to a terbinafine-resistant novel species in the Trichophyton mentagrophytesT. interdigitale complex has been ongoing in India, and it has spread to several European countries. The objective of this study was to investigate the molecular background of the squalene epoxidase () gene in order to understand the risk of emergence and spread of multiresistance in dermatophytes. Antifungal susceptibility to fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, naftifine, sertaconazole, and terbinafine was tested in 135 isolates from India, China, Australia, Germany, and The Netherlands. Based on the latest taxonomic insights, strains were identified as three species: T. mentagrophytes ( = 35), T. indotineae ( = 64, representing the Indian clone), and T. interdigitale ( = 36). High MICs of terbinafine (>16 mg/liter) were found in 34 (53%) isolates. These isolates showed an amino acid substitution in the 397th position of the gene. Elevated MICs of terbinafine (0.5 mg/liter) were noted in 2 (3%) isolates; these isolates lead to PheVal and LeuSer of the gene. The stability of the effect of the mutations was proven by serial transfer on drug-free medium. LysAsn and LeuPhe substitutions were found in susceptible T. mentagrophytes strains. The PheLeu/AlaThr double mutant showed higher MIC values for triazoles. High MICs of terbinafine are as yet limited to and are unlikely to be distributed throughout the T. mentagrophytes species complex by genetic exchange.