AUTHOR=Bednarek Aneta , Barczyk-Woznicka Olga , Karkowska-Kuleta Justyna , Pyza Elzbieta M., Rapala-Kozik Maria , Satala Dorota TITLE=Divergence in surface protein exposure between reference and clinical-derived Candida glabrata (Nakaseomyces glabratus) strains (CBS138 vs. BG2) – a preliminary proteomic perspective JOURNAL=Acta Biochimica Polonica VOLUME=Volume 73 - 2026 YEAR=2026 URL=https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2026.16376 DOI=10.3389/abp.2026.16376 ISSN=1734-154X ABSTRACT=Candida glabrata (currently classified as Nakaseomyces glabratus) is an opportunistic fungal pathogen notable for its intrinsic antifungal tolerance and ability to persist in host environments. Although strain CBS138 has served as the principal model for genetic and functional studies, accumulating evidence indicates substantial intraspecies diversity that may shape virulence, immune interactions and stress adaptation. In particular, the widely used clinical isolate BG2 differs from CBS138 in genome structure, adhesin regulation and macrophage survival, yet the extent to which these differences are reflected at the fungal cell surface remains unknown. Here, we present a comparative characterization of the surface-exposed proteomes (surfaceomes) of CBS138 and BG2 across three biologically relevant growth conditions: YPD-grown yeast-like cells, RPMI-cultured planktonic aggregates and RPMI-formed biofilms. Using trypsin shaving combined with LC–MS/MS, we identified pronounced strain- and condition-dependent differences in surface protein composition, encompassing adhesins, yapsin proteases and selected moonlighting proteins. Whereas CBS138 showed greater representation of adhesion- and interaction-related surface proteins, BG2 preferentially displayed proteins associated with cell-wall architecture and remodelling, consistent with distinct surface-mediated adaptive strategies. Transmission electron microscopy revealed condition-dependent differences in cell-wall thickness in both strains, with BG2 displaying a broader range of values and the highest thickness under biofilm conditions, providing structural context for variation in protease accessibility and surface-protein detectability. Collectively, our findings highlight substantial surfaceome plasticity in C. glabrata and underscore the importance of considering intraspecies diversity when interpreting host–pathogen interactions and fungal virulence pathways.