Nuclear and Mitochondrial Genome Characterization of a Clinical Isolate of the Emerging Pathogen Wickerhamomyces anomalus

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Wickerhamomyces anomalus, also known as Candida pelliculosa, has emerged as an opportunistic yeast implicated in invasive infections and hospital outbreaks, especially among neonatal and immunocompromised individuals. Despite its clinical relevance, the genomic determinants underlying the pathogenesis and virulence remain poorly understood. Here, we report the first high-quality nuclear and complete mitochondrial genome derived from a clinical isolate of W. anomalus. The nuclear genome spans 13.9 Mb with 34.5% GC content and contains 6305 protein-coding genes, 8235 coding sequences, and 147 tRNAs, with 98.1% completeness by BUSCO. The mitochondrial genome (47.6 kb) encodes 19 protein-coding genes, 26 tRNAs, two rRNAs, and exhibits atypical structural features, including inverted repeats and three LAGLIDADG (LD)-type homing endonuclease ORFs. We further assembled mitochondrial genomes from 12 additional clinical isolates and compared them with CpEC_UEES and publicly available W. anomalus mitochondrial genomes. Size, gene content and synteny were highly conserved, with structural variations largely limited to the LD ORFs. Phylogenetic analysis of 48 nuclear assemblies showed that clinical isolates are not monophyletic but are interspersed with environmental isolates across the tree. These assemblies provide the first comprehensive clinical genomic resources for W. anomalus, offering a reference framework for comparative and functional studies. The genomic innovations, together with a high content of repetitive and non-coding elements, suggest enhanced plasticity that may underpin metabolic flexibility and survival under host-associated stresses. These rearrangements represent an underappreciated mechanism of adaptation in emerging fungal pathogens, contributing to the clinical relevance of W. anomalus. These genomic resources facilitate rigorous comparative analyses to identify determinants of pathogenicity, virulence, and antifungal resistance, accelerating the development of improved diagnostics, surveillance, and management strategies for W. anomalus infections