Resolving phylogenetic relationships within theTrichophyton mentagrophytescomplex: a RADseq genomic approach challenges status of “terbinafine-resistant”Trichophyton indotineaeas distinct species
Authors: Švarcová Michaela , Kolařík Miroslav , Li Yuanjie , Tsui Clement Kin Ming , Hubka Vít 
Published: December 2024

TheTrichophyton(T.)mentagrophytescomplex 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, particularlyT. indotineaeandT. 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 ofT. mentagrophytescomplex, 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 toT. mentagrophytes(includingT. indotineae) andT. interdigitale. Our results challenge the species status ofT. indotineae, because of insufficient genetic divergence fromT. mentagrophytes. Therefore, we propose designatingT. indotineaeasT. mentagrophytesvar.indotineae(orT. mentagrophytesITS genotype VIII) to avoid further splitting of the complex and taxonomic inflation. AlthoughT. interdigitaleshows 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. mentagrophytesvar.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.

Importance

Accurate identification of the causal agent is essential for managing dermatophytosis. However, the taxonomy of theT. mentagrophytescomplex has been plagued by inconsistencies and misidentifications. Our high-resolution SNP analysis revealed thatT. indotineae, often associated with terbinafine resistance, is not genetically distinct enough fromT. mentagrophytesto warrant species status. This finding has significant implications for both taxonomy and clinical practice. We suggest consolidating the taxonomy underT. mentagrophytes, with variety ranks forT. indotineaeandT. interdigitale. This simplified system will reduce confusion and ensure the comparability of historical and emerging epidemiological data under the umbrella name ofT. 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.