Phenotypic and Molecular Characterization of <i>Naganishia uzbekistanensis</i> : Diagnostic Challenges and Antifungal Resistance Profile

BACKGROUND: Naganishia (N.) uzbekistanensis is a rare basidiomycetous yeast within the family Filobasidiaceae, widely distributed in environmental niches, with very limited clinical data available. Its clinical and microbiological features remain poorly understood, posing diagnostic challenges in clinical microbiology laboratories. METHODS: We describe a pulmonary infection caused by N. uzbekistanensis strain CY11558 and present an expanded laboratory investigation of this previously reported clinical strain. The strain was analyzed using a comprehensive laboratory workflow that included conventional culture, light microscopy, scanning electron microscopy (SEM), and molecular identification based on rDNA sequencing. Phylogenetic analysis was conducted to assess the genetic relationship with reference strains. Antifungal susceptibility testing and in vitro Titan cell induction assays were also performed. RESULTS: Conventional MALDI-TOF MS failed to identify the strain, while rDNA sequencing confirmed N. uzbekistanensis. Cryptococcal antigen testing yielded a weakly positive result with the pure culture supernatant, while the patient's serum remained negative. The strain showed markedly elevated MICs for echinocandins, flucytosine, and fluconazole, whereas MICs for voriconazole, itraconazole, and amphotericin B were comparatively low. Microscopic examination revealed round yeast cells without pseudohyphae. SEM showed globular cells enveloped by a fibrillar network. Titan cell formation was not observed. Phylogenetic analysis demonstrated intraspecies variability without geographic association. CONCLUSIONS: This study provides comprehensive phenotypic, including antifungal susceptibility, and molecular characterization of N. uzbekistanensis, emphasizing the need for molecular tools in identifying uncommon yeasts. The findings expand current understanding of its morphological and resistance traits and highlight potential diagnostic challenges in clinical laboratories.