Mutation in the Squalene epoxidase gene of Trichophyton interdigitale and Trichophyton rubrum associated with allylamine resistance [PublishAheadOfPrint]

Dermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite availability of several effective antifungal agents against dermatophytes, the incidence of chronic infection, re-infection and treatment failures are on the rise. Trichophyton rubrum and Trichophyton interdigitale are the two frequent clinical isolates in India. Consecutive patients (n=195) with suspected dermatophytosis during second half of 2014 were included in this study. Patients were categorized into relapse and new cases according to standard definitions. Antifungal susceptibility testing of the isolated Trichophyton species (n=127) was carried out against 12 antifungal agents —fluconazole, voriconazole, itraconazole, ketoconazole, sertaconazole, clotrimazole, terbinafine, naftifine, amorolfine, ciclopirox olamine, griseofulvin and luliconazole. Squalene epoxidase gene was evaluated for mutation (if any) in 15 - T. interdigitale and five - T. rubrum isolates exhibiting high minimum inhibitory concentration to terbinafine. T1189C mutation was observed in four T. interdigitale and two T. rubrum isolates. This transition leads to the substitution of amino acid phenylalanine to leucine in 397^th position of the squalene epoxidase enzyme. In homology modelling the mutant residue was smaller than wild type and positioned in the dominant site of squalene epoxidase during drug interaction, which may lead to failure to block ergosterol biosynthesis pathway by the antifungal drug.

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