Trichophyton mentagrophytes Complex in Onychomycosis: A Retrospective Study of Internal Transcribed Spacer Genotypes and Squalene Epoxidase Gene Mutations.

Increasing attention has been given to the Trichophyton mentagrophytes complex as an agent of dermatophytosis. Despite technical challenges in differentiating lineages within this complex-which necessitates genotyping of the internal transcribed spacer (ITS) region-surveillance efforts are warranted due to the emergence of novel pathogens and rise in antifungal resistance. In North America, although studies have examined the molecular epidemiology of the T. mentagrophytes complex isolated from skin, there is scant information regarding this complex for the onychomycosis population. In this study, 516 clinical nail specimens were subjected to multiplex real-time PCR detection of the T. mentagrophytes complex followed by genotyping of the ITS1-5.8S-ITS2 region; squalene epoxidase (SQLE) gene mutations were also detected. All specimens were identified as T. mentagrophytes var. interdigitale belonging to one of five ITS genotypes (I, II, XI, XXIX, XXX). Genotype II was the most common (76% [392/516]) followed by genotype I (2.1% [11/516]), genotype XI (0.6% [3/516]), genotype XXIX (0.4% [2/516]) and genotype XXX (0.2% [1/516]). Notably, ITS genotypes XXIX and XXX are newly confirmed genotypes, which demonstrated stability and capacity for human-to-human transmission, evidenced by their earlier report and isolation in Australia. SQLE mutations, in particular Leu393Phe and Phe397Leu, were detected in ITS genotypes I and II, reflecting a higher risk of acquiring terbinafine resistance. The findings of this study serve to update our current understanding of the T. mentagrophytes complex.