Abstract
<title>Abstract</title> <p> Background Vulvovaginal candidiasis (VVC) is among the most prevalent fungal infections affecting women of reproductive age, with approximately 75% experiencing at least one episode during their lifetime. Azole antifungals remain the mainstay of treatment; however, growing resistance, particularly to fluconazole, poses a serious clinical challenge. Mutations in ergosterol biosynthesis genes, especially <italic>erg2</italic> and <italic>erg11</italic> , are central to reduced antifungal susceptibility, yet molecular resistance data from Nigeria remain limited. This study characterized <italic>Candida</italic> species isolated from symptomatic women in Ibadan, determined their azole susceptibility profiles, and investigated mutations in <italic>erg2</italic> and <italic>erg11</italic> genes alongside their phylogenetic relationships with globally deposited strains. Methods High vaginal swabs were collected from 180 symptomatic women attending the family planning unit of Adeoyo Maternity Hospital, Ibadan, Nigeria. <italic>Candida</italic> species were identified using germ tube testing and CHROMagar. Antifungal susceptibility to fluconazole, itraconazole, and voriconazole was determined by disc diffusion following CLSI 2016 standards, with minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) established by broth microdilution. Molecular characterization was performed by PCR amplification and bidirectional sequencing of the ITS region, <italic>erg2</italic> , and <italic>erg11</italic> open reading frames. Sequences were aligned against the NCBI database using BLAST, and phylogenetic trees were constructed using MEGA 7 and annotated with Interactive Tree of Life (iTOL). Results <italic>Candida</italic> species were isolated from 35.0% of participants. <italic>Candida albicans</italic> was the predominant species (50.8%), followed by <italic>C. glabrata</italic> (30.2%), <italic>C. dubliniensis</italic> (15.8%), and <italic>C. tropicalis</italic> (3.1%). MIC values ranged from 3.125 to 50 mg/mL. Voriconazole demonstrated the highest in vitro activity (83.0% susceptibility), compared with itraconazole (70.0%) and fluconazole (26.6%). Fluconazole resistance was recorded in 56.6% of isolates. Key mutations identified in the <italic>erg11</italic> gene of <italic>C. albicans</italic> included a cytosine-to-adenine substitution at position 158981 (158981C > A), alongside multiple additional frameshift-associated variants. In <italic>C. dubliniensis</italic> isolates C16 and C3, the substitutions Q108F and Y132F were detected, respectively. Phylogenetic analysis demonstrated 100% sequence similarity between study isolates and NCBI-deposited strains from the USA, India, Kuwait, Iran, and Vietnam. Conclusions This study provides the first detailed molecular characterization of <italic>erg2</italic> and <italic>erg11</italic> mutations in azole-resistant <italic>Candida</italic> spp. from vulvovaginal candidiasis cases in Nigeria. The high prevalence of fluconazole resistance and the detection of clinically relevant gene mutations underscore the urgent need for routine molecular surveillance of antifungal resistance in Nigerian clinical settings. These findings carry direct implications for empirical antifungal prescribing, local treatment guidelines, and public health stewardship programmes. </p>