Resolving phylogenetic relationships within the Trichophyton mentagrophytes complex: a RADseq genomic approach challenges status of "terbinafine-resistant" Trichophyton indotineae as distinct species

Abstract

The Trichophyton (T.) mentagrophytes complex encompasses common dermatophytes causing superficial mycoses in humans and animals. The taxonomy of the complex is unstable, with conflicting views on the species status of some taxa, particularly T. indotineae and T. interdigitale. Due to presence of intermediate genotypes, MALDI-TOF MS and ITS rRNA sequencing cannot accurately distinguish all taxa in the complex, potentially contributing to clinical misdiagnoses. In order to resolve the phylogenetic relationship of T. mentagrophytes complex, we employed Restriction Site Associated DNA Sequencing (RADseq) to produce a high-resolution single nucleotide polymorphism (SNP) dataset from 95 isolates. The SNP-based analyses indicated the presence of two major genetic clusters, corresponding to T. mentagrophytes (including T. indotineae) and T. interdigitale. Our results challenge the species status of T. indotineae, because of insufficient genetic divergence from T. mentagrophytes. Therefore, we propose designating T. indotineae as T. mentagrophytes var. indotineae (or T. mentagrophytes ITS genotype VIII) to avoid further splitting of the complex and taxonomic inflation. Although T. interdigitale shows clearer genetic differentiation, its separation is incomplete and identification of some isolates is ambiguous when using routine methods, leading us to consider it a variety as well: T. mentagrophytes var. interdigitale. We recommend using T. mentagrophytes as the overarching species name for all complex isolates. Where precise molecular identification is possible, the use of variety ranks is encouraged. Since identical resistance mechanisms are not specific to any genotype or dermatophytes species, identifying antifungal resistance is more important than differentiating closely related genotypes or populations. ImportanceAccurate identification of the causal agent is essential for managing dermatophytosis. However, the taxonomy of the T. mentagrophytes complex has been plagued by inconsistencies and misidentifications. Our high-resolution SNP analysis revealed that T. indotineae, often associated with terbinafine resistance, is not genetically distinct enough from T. mentagrophytes to warrant species status. This finding has significant implications for both taxonomy and clinical practice. We suggest consolidating the taxonomy under T. mentagrophytes, with variety ranks for T. indotineae and T. interdigitale. This simplified system will reduce confusion and ensure the comparability of historical and emerging epidemiological data under the umbrella name of T. mentagrophytes. By shifting the focus to antifungal resistance detection rather than complex taxonomic distinctions, this reclassification will streamline clinical decision-making. Notably, identical resistance mechanisms are not exclusive to ITS genotype VIII (T. indotineae) but also occur in other genotypes and dermatophyte species, albeit with varying prevalence.