ERG11 gene mutation analysis in resistant candida species isolated from vulvovaginal Candidiasis cases

Vulvovaginal candidiasis is a commonly encountered fungal infection in women and may exhibit resistance to antifungal agents. Candida albicans is responsible for approximately 75% of Candida-related infections. Azole antifungals are considered the first-line therapeutic option in the treatment of such infections. These agents act by inhibiting the activity of lanosterol 14-α-demethylase (ERG11p), an enzyme encoded by the ERG11 gene, which plays a crucial role in ergosterol biosynthesis. However, in recent years, resistance to antifungal agents—particularly those in the azole class—has been on the rise. In this study, a total of 39 clinical Candida albicans isolates obtained from vaginal swab cultures submitted to the Medical Microbiology Laboratory of Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospital were included. The isolates were identified using MALDI-TOF MS, and the aim was to investigate mutations in the ERG11 gene using molecular methods. All mutations detected in this study have previously been reported in the literature; however, their association with azole resistance remains inconclusive. Further studies are needed to elucidate the precise molecular mechanisms involved in antifungal resistance. Vulvovaginal candidiasis is a commonly encountered fungal infection in women and may exhibit resistance to antifungal agents. Candida albicans is responsible for approximately 75% of Candida-related infections. Azole antifungals are considered the first-line therapeutic option in the treatment of such infections. These agents act by inhibiting the activity of lanosterol 14-α-demethylase (ERG11p), an enzyme encoded by the ERG11 gene, which plays a crucial role in ergosterol biosynthesis. However, in recent years, resistance to antifungal agents—particularly those in the azole class—has been on the rise. In this study, a total of 39 clinical Candida albicans isolates obtained from vaginal swab cultures submitted to the Medical Microbiology Laboratory of Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospital were included. The isolates were identified using MALDI-TOF MS, and the aim was to investigate mutations in the ERG11 gene using molecular methods. In our study, 394 TAT-CAT 132Tyr-His (Y132H) mutations were detected in 31 (79%) of 39 C. albicans strains identified from vaginal swab cultures using MALDI-TOF MS. 346 GAT-GAA 116Asp-Glu (D116E) mutations were found in all 39 isolates (100%). In our study, D116E mutations were found in all 39 C. albicans samples obtained from VVC cases (100%) and Y132H mutations in 79%. The co-occurrence of these two mutations (Y132H and D116E) was phenotypically correlated with high-level FLU resistance in these strains, suggesting that the co-occurrence of these two resistances is indeed resistant to these strains. All mutations detected in this study have previously been reported in the literature; however, their association with azole resistance remains inconclusive. Further studies are needed to elucidate the precise molecular mechanisms involved in antifungal resistance. September 2025, 61 pages. Keywords: Candida albicans, ERG11 gene, antifungal, vulvovaginal candidiasis