A-Z Index × Submit A-Z Index × Submit A-Z Index Search Dropdown × Submit Facebook Twitter LinkedIn Syndicate Emerging Infectious Disease journal ISSN: 1080-6059 Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.
Trichophyton fungal infections are common and increasingly complicated by terbinafine resistance. To support accurate molecular identification and resistance profiling, we provide a validated dataset of full-length squalene epoxidase ( sqle ) gene sequences from 493 Trichophyton isolates representing 18 species, addressing limited availability and misannotation of sqle sequences in public databases, particularly within the T. mentagrophytes complex. On the basis of that dataset, we designed 2 Sanger sequencing assays for simultaneously identifying species and detecting resistance-associated mutations. One targets the full-length gene, whereas the other amplifies a short region capturing all key resistance hotspots and species-specific single-nucleotide polymorphisms. The partial assay was evaluated on 66 clinical specimens and enabled clinically relevant species identification without internal transcribed spacer sequencing, supporting culture-independent detection. Of note, this approach differentiates T. indotineae from closely related species, overcoming a key diagnostic limitation and supporting clinical decision-making, surveillance, and management of resistant infections, despite limited resolution within certain species complexes.
Trichophyton species fungi cause infections of the skin, nails, and hair and are estimated to affect 20%–25% of persons during their lifetimes ( 1 ). Clinical manifestations include pruritus, erythema, scaling, alopecia, and inflammation ( 2 ). Although infections are often considered minor, chronic or extensive dermatophytosis can cause considerable illness, involving prolonged treatment, increased healthcare use, and impaired quality of life ( 3 ). The recent rising prevalence of terbinafine-resistant Trichophyton strains is associated with therapeutic failure, underscoring the need for rapid and reliable diagnostics to detect resistance, guide therapy, and thereby limit transmission ( 4 – 6 ).
Traditional culture-based diagnostics are slow and exhibit suboptimal sensitivity, especially in onychomycosis or after antifungal therapy ( 7 ). Molecular assays targeting the internal transcribed spacer (ITS) region of ribosomal DNA are widely adopted because of its high copy number and potential for improved identification ( 8 ). However, limited sequence variation in this region hinders reliable discrimination among closely related Trichophyton species, particularly within the T. mentagrophytes complex ( 9 , 10 ). Of note, T. indotineae , an emerging and often terbinafine-resistant species within this complex, might be misidentified by certain ITS-based diagnostic kits and commercial platforms such as DermaGenius 2.0 (PathoNostics, https://www.pathonostics.com ) ( 11 – 16 ). Those challenges are further compounded by recent taxonomic revisions and inconsistencies in available reference databases ( 9 , 12 ).
The sqle gene (alternatively, erg1 ) encodes squalene epoxidase (SQLE), the molecular target of terbinafine. Mutations at conserved hotspot positions (e.g., L393, F397, F415, and H440) reduce drug binding while preserving enzymatic function, thereby conferring terbinafine…