Molecular Characterization and Preliminary NGS Profiling of Terbinafine-Resistant Trichophyton indotineae Isolates in
Deborah Cruciani1, Manuela Papini2, Luigi Pisano3
1Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche "Togo Rosati", 06126 Perugia, Italy.
Abstract:
Trichophyton indotineae is an emerging dermatophyte associated with extensive, chronic, recalcitrant, and frequently terbinafine-resistant dermatophytosis worldwide. In this study, 30 T. indotineae strains isolated in Italy were investigated. The isolates were obtained from patients originating from Asian countries, from patients from other countries, and from Italian patients who reported no travel outside Italy in the preceding years. Clinical isolates were identified by internal transcribed spacer (ITS) sequencing and analyzed to assess the occurrence and molecular basis of terbinafine resistance. Terbinafine resistance was detected in 18 strains (60%) using a real-time PCR assay. Sequencing of the squalene epoxidase (SQLE) gene revealed mutations associated with resistance, including L393S in nine strains and F397L in another nine strains. NGS analysis confirmed two terbinafine-resistant strains carrying the L393S and F397L mutations, respectively, and detected the A448T mutation in one terbinafine-susceptible strain. These findings demonstrate the presence of terbinafine-resistant T. indotineae across five regions of Italy and confirm the occurrence of SQLE mutations previously linked to antifungal resistance. Data obtained also support a link with endemic Asian areas, other than suggesting the possible occurrence of autochthonous transmission in Italy.
Insights
Emerging dermatophyte Trichophyton indotineae shows high terbinafine resistance in Italy, linked to SQLE gene mutations. This antifungal resistance may stem from Asian origins or local transmission.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
Background:
- Trichophyton indotineae is an emerging fungal pathogen causing widespread, persistent dermatophytosis.
- This infection is frequently resistant to terbinafine, a common antifungal treatment.
Purpose of the Study:
- To investigate the prevalence and molecular basis of terbinafine resistance in Trichophyton indotineae strains isolated in Italy.
- To determine the origin and transmission patterns of resistant strains.
Main Methods:
- Identification of 30 T. indotineae isolates using internal transcribed spacer (ITS) sequencing.
- Assessment of terbinafine resistance via real-time PCR.
- Analysis of squalene epoxidase (SQLE) gene mutations using sequencing and next-generation sequencing (NGS).
Main Results:
- Terbinafine resistance was detected in 60% (18/30) of the Italian isolates.
- Common resistance-associated SQLE mutations, L393S and F397L, were identified in resistant strains.
- NGS confirmed these mutations and identified an additional mutation (A448T) in a susceptible strain.
Conclusions:
- Terbinafine-resistant T. indotineae is present across Italy, with SQLE mutations being a key factor.
- Findings suggest a link to endemic Asian regions and potential autochthonous transmission within Italy.
