Terbinafine resistance is associated with newly developed point mutations in squalene epoxidase gene in Trichophyton rubrum and T. mentagrophytes/T. indotineae species complex

Abstract

Abstract The prevalence of dermatophytosis has increased in recent years due to a rise in resistance of etiologic dermatophytes to terbinafine which could be attributed in part to point mutation in the squalene epoxidase (SQLE) gene. In this study, the point mutation in the SQLE gene was studied in Trichophyton rubrum and T. mentagrophytes/T. indotineae species complex as two main causative agents of dermatophytosis. Antifungal susceptibility of clinical isolates of T. rubrum (n = 27) and T. mentagrophytes/T. indotineae (n = 56) was assessed using the M38-3rd edition CLSI method. The SQLE gene and ITS region were sequenced in all the fungal strains, and terbinafine resistant strains were characterized by mutation sites and the genotype. The results demonstrated that in T. rubrum, the minimum inhibitory concentration of terbinafine, was 0.03 µg/ml and GM was equal to 0.02. In T. mentagrophytes complex, MIC50 and MIC90 were 0.03 and 1.0 µg/ml and GM was equal to 0.04 µg/ml. Four out of five resistant strains were T. indotineae harboring the mutations F397L and Q408L; while the last one was T. mentagrophytes genotype VII which harbors the F397L mutation. T. indotineae was the prominent causative agent of terbinafine resistance with 80% of isolates and T. mentagrophytes genotype VII was introduced as a new genotype in terbinafine resistance T. mentagrophytes complex. Our findings further substantiate the importance of antifungal susceptibility testing in selecting the choice drug for effective treatment of dermatophytosis and highlight the importance of screening dermatophyte species for point mutations responsible for newly developed resistance strains to improve current knowledge to overcome infections caused by resistant species.