High genomic and phenotypic diversity among Candida dubliniensis isolates from the oral cavity of persons living with HIV

Abstract

The opportunistic yeast pathogen Candida dubliniensis is frequently misidentified as its closest relative Candida albicans, due to their high phenotypic similarity. Although Candida dubliniensis is an important cause of fungal infections, especially in the oral cavities of immunocompromised patients, its phenotypic and genomic variability remains poorly understood. We addressed this knowledge gap by performing a comprehensive phenotypic and genomic characterization of 33 C. dubliniensis oral isolates from people living with HIV in Argentina. Our results uncovered significant phenotypic heterogeneity--observed both inter- and intra-patient--impacting clinically relevant traits such as drug susceptibility, stress sensitivity, filamentation, and hypoxic growth. Our isolates expanded the previously known MLST-based genetic diversity of the species. Leveraging whole-genome sequencing, we resolved intricate evolutionary relationships, proposed a more robust MLST scheme for future typing, and identified potential antifungal resistance-causing variants. Collectively, this work represents the most comprehensive population genomics characterization of C. dubliniensis to date, establishing a foundation for improved surveillance and diagnostic strategies to fully define its role in both oral and systemic infections. Author SummaryIn this study we uncover hidden genetic and morphological diversity in Candida dubliniensis, a poorly known opportunistic yeast pathogen related to Candida albicans, by characterising a collection of oral isolates from persons living with HIV in Argentina. Our findings provide the most detailed genetic and phenotypic snapshot of this pathogen to date, providing a much-needed foundation to develop better diagnostic tools and effective surveillance strategies to address infections caused by this overlooked threat.