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Updated: Dec 23, 2025
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study
Andreas Ebert1,2, Michel Monod3, Karine Salamin3
1Medizinische Fakultät, Universität Leipzig, Leipzig, Germany.
Background:
An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario.
Objectives:
The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene.
Patients/Methods:
We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE.
Results:
Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole.
Conclusions:
The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.
Insights
Recalcitrant dermatophytosis is rising in India, with 71% of fungal isolates showing terbinafine resistance. Key mutations in the squalene epoxidase gene are linked to this drug resistance.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Increasing prevalence of difficult-to-treat fungal skin infections (dermatophytosis) in India.
- Suspected role of antifungal drug resistance in treatment failures.
Purpose of the Study:
- Determine in vitro resistance of dermatophytes to terbinafine, itraconazole, and voriconazole.
- Identify mutations in the fungal squalene epoxidase (SQLE) gene associated with resistance.
Main Methods:
- Analysis of 402 skin samples from diverse Indian locations.
- Microbiological and molecular identification of fungal species.
- Antifungal susceptibility testing and SQLE gene sequencing.
Main Results:
- Trichophyton mentagrophytes (ITS Type VIII) was the predominant species (78%).
- High terbinafine resistance (71%) observed in isolates.
- Prevalence of Phe397Leu substitution in SQLE of resistant T. mentagrophytes (91%); novel Ser395Pro and Ser443Pro substitutions identified.
Conclusions:
- Alarming terbinafine resistance rates in Indian dermatophytes necessitate monitoring.
- SQLE gene substitutions (Leu393-Ser443) show potential as future resistance markers.
