Molecular analysis of squalene epoxidase gene mutations in Trichophyton rubrum from clinical onychomycosis samples in South Korea

Trichophyton rubrum is the primary causative pathogen of onychomycosis, and terbinafine remains the first-line treatment for both oral and topical therapy. However, increasing reports of terbinafine resistance-associated mutations in T. rubrum from India, Europe, and other parts of Asia have raised global concern. This study aimed to investigate mutations in the squalene epoxidase (SQLE) gene in T. rubrum from onychomycosis samples in South Korea. Between August 2021 and November 2023, toenail specimens from patients with KOH-positive fungal microscopy were collected from six hospitals. Fungal species were identified through internal transcribed spacer (ITS) sequencing, and mutations in the squalene epoxidase (SQLE) gene were analyzed. Among 388 clinical samples, 231 (59.5%) were ITS PCR-positive. Sanger sequencing identified T. rubrum in 185 samples (80.5%), followed by Candida parapsilosis (7), T. mentagrophytes (4), T. violaceum (2), and various other fungi (24). Among 106 SQLE-positive T. rubrum clinical samples, 3.8% (4/106) harbored resistance-associated mutations, including Phe397Leu (n = 3) and Leu393Phe (n = 1), while the remaining 102 samples showed wild-type SQLE sequences at these positions. These findings demonstrate the presence of SQLE mutations in T. rubrum from onychomycosis samples in South Korea. Further studies incorporating fungal isolation and antifungal susceptibility testing are needed to determine their clinical significance.