In vitro antifungal susceptibility testing and point mutations in the squalene epoxidase gene of Trichophyton mentagrophytes/interdigitale complex from China, India and Australia
During the past decade, a severe outbreak has taken place in India of terbinafine-resistant strains in the Trichophyton mentagrophytes / T. interdigitale complex. In this study, a total of 145 isolates of the complex were collected from India, China, Australia, Germany, and The Netherlands. Antifungal susceptibility testing of the isolates was carried out for itraconazole, fluconazole, ketoconazole, sertaconazole, miconazole, terbinafine, naftifine, and griseofulvin according to modified EUCAST 9.3.1 guidelines. Based on the latest taxonomic insights, the strains are classified in three species: T. mentagrophytes s. str. (n=39), Trichophyton indotineae (n=72 representing the Indian clone) and T. interdigitale s. str. (n=34). High (>16 mg/L, cut-off) minimum inhibitory concentrations (MICs) to terbinafine were noted in 34 (47.2%) T. indotineae isolates. C to A and T to C transversions were responsible for amino acid substitution in 397th position of the SE gene in high terbinafine-resistant isolates. Moderate (0.5 mg/L, cut-off) MICs to terbinafine were noted in 2 (2.78%) T. indotineae isolates. C to A and T to C transversions were responsible for amino acid substitution in 415th and 393th positions of the SE gene in moderate terbinafine resistant isolates. Low (0.125 mg/L, cut-off) MICs to terbinafine were noted in 8 (11.1%) T. mentagrophytes and T. indotineae strains; no mutation of the SE gene was found. Antifungal susceptibility testing was made again in these high terbinafine resistant isolates after replication for 10 times in drug-free PDA medium; no difference was found compared previous results.