Emergence of antifungal resistance in the Trichophyton mentagrophytes clinical strains

Trichophyton species are the main cause for superficial fungal infections globally. This study aimed to assess the susceptibility of Trichophyton mentagrophytes complex to commonly used antifungals, and to screen for genetic changes that potentially contributing to antifungal resistance. A set of 131 T. mentagrophytes complex isolates (64 T. mentagrophytes, 65 T. interdigitale and 2 T. indotineae) collected in China between 2001 and 2024 were included. MICs for terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole were defined using a standard broth microdilution method. MIC50, MIC90 and the geometric mean of MICs (GM) were calculated. The wild type upper limits (WT-ULs) were calculated to differentiate wild-type (WT-ULs) from non-wild-type (NWT-ULs) isolates. Mutations in SQLE, Cyp51A, and Cyp51B gene and corresponding amino acid substitutions were assessed. The MIC50 and MIC90 values for azoles were similar between T. interdigitale and T. mentagrophytes, while terbinafine MIC50 was higher for T. mentagrophytes. The WT-ULs 97.5% were identical for most drugs (2mg/L), except TBF, which is higher in T. mentagrophytes (0.0625mg/L), while MIC of VOR is higher in T. interdigitale (1 mg/L). Twenty-seven T. interdigitale strains were classified as NWT-UL of TBF, and two T. indotineae was found to be terbinafine resistant, associated with mutations in the SQLE gene (forming Leu393Ser, Phe397Leu, and Ala448Thr). For CYP51A, we identified 49 SNPs and 27 amino acid alterations, while 9 CYP51B sequence types and 4 amino acid substitutions were found. This provides an important clue for understanding the global epidemic emergence of the TBF-resistant species within the T. mentagrophytes complex.