Emerging terbinafine-resistant Trichophyton indotineae between 2018 and 2023: a multinational genomic epidemiology study
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Trichophyton species cause the greatest burden of dermatophytosis worldwide, with the Trichophyton mentagrophytes species complex being particularly associated with the emergence of new aggressive infections. One emerging species, Trichophyton indotineae is notable for its clinical resistance to terbinafine antifungal treatment and rapid global spread. In this study we aim to characterise the epidemiology of this emerging pathogen using genomics.
Methods
In this retrospective genomic epidemiology study, to better understand the epidemiology of this disease, we sourced isolates collected from patients with severe cases of dermatophytosis (identified either by internal transcribed spacer sequencing or phenotypic characterisation) in the UK, Ireland, France, Canada, and India for the period 2014–23, including the T indotineae type strain from Japan. We used whole-genome sequencing to confirm 90 isolates were T indotineae, and antifungal susceptibility testing to assess susceptibility to terbinafine.
Findings
103 cases of severe dermatophytosis caused by Trichophyton species collected between 2018 and 2023 in the UK, France, Canada, Ireland, and India were included in this study. Susceptibility testing indicated that 63 (70%) of 90 T indotineae isolates were resistant to terbinafine (minimum inhibitory concentration [MIC] ≥0·5 mg/L). Pairwise genetic distances showed very high identity with only 147 (range 1–414) single-nucleotide polymorphisms (SNPs) separating isolates that were nested within a monophyletic phylogeny, supporting a single evolutionary origin of T indotineae. Genome-wide analyses identified multiple non-synonymous SNPs in SQLE (ERG1), the squalene epoxidase target of terbinafine, that were associated with terbinafine in vitro resistance of 0·5 mg/L or higher. However, six isolates exhibited high MIC values without SQLE mutations, suggesting the presence of alternative resistance mechanisms.
Interpretation
That no clear geographical clustering of isolates was observed confirms the rapid transcontinental spread of T indotineae from its likely centre of diversity in Asia. Our findings highlight the importance of better genomic surveillance to understand and manage this severe and rapidly emerging terbinafine-resistant dermatophyte.
Trichophyton species cause the greatest burden of dermatophytosis worldwide, with the Trichophyton mentagrophytes species complex being particularly associated with the emergence of new aggressive infections. One emerging species, Trichophyton indotineae is notable for its clinical resistance to terbinafine antifungal treatment and rapid global spread. In this study we aim to characterise the epidemiology of this emerging pathogen using genomics.
Methods
In this retrospective genomic epidemiology study, to better understand the epidemiology of this disease, we sourced isolates collected from patients with severe cases of dermatophytosis (identified either by internal transcribed spacer sequencing or phenotypic characterisation) in the UK, Ireland, France, Canada, and India for the period 2014–23, including the T indotineae type strain from Japan. We used whole-genome sequencing to confirm 90 isolates were T indotineae, and antifungal susceptibility testing to assess susceptibility to terbinafine.
Findings
103 cases of severe dermatophytosis caused by Trichophyton species collected between 2018 and 2023 in the UK, France, Canada, Ireland, and India were included in this study. Susceptibility testing indicated that 63 (70%) of 90 T indotineae isolates were resistant to terbinafine (minimum inhibitory concentration [MIC] ≥0·5 mg/L). Pairwise genetic distances showed very high identity with only 147 (range 1–414) single-nucleotide polymorphisms (SNPs) separating isolates that were nested within a monophyletic phylogeny, supporting a single evolutionary origin of T indotineae. Genome-wide analyses identified multiple non-synonymous SNPs in SQLE (ERG1), the squalene epoxidase target of terbinafine, that were associated with terbinafine in vitro resistance of 0·5 mg/L or higher. However, six isolates exhibited high MIC values without SQLE mutations, suggesting the presence of alternative resistance mechanisms.
Interpretation
That no clear geographical clustering of isolates was observed confirms the rapid transcontinental spread of T indotineae from its likely centre of diversity in Asia. Our findings highlight the importance of better genomic surveillance to understand and manage this severe and rapidly emerging terbinafine-resistant dermatophyte.
Date Issued
2026-02-01
Date Acceptance
2025-10-02
Citation
The Lancet Microbe, 2026, 7 (2)
ISSN
2666-5247
Publisher
Elsevier
Journal / Book Title
The Lancet Microbe
Volume
7
Issue
2
Copyright Statement
© 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Publication Status
Published
Article Number
101273
Date Publish Online
2026-01-22