Candida albicans metabolic adaptation gene SFU1 regulates dual-species biofilm with Streptococcus mutans

Objective To investigate the role of the iron-sulfur cluster assembly factor SFU1 in the virulence-related traits of Candida albicans , particularly its function within the cariogenic cross-kingdom biofilm formed with Streptococcus mutans . Methods The SFU1 deletion and complemented strains were constructed. Their effects on growth, acid production, morphogenesis, metabolic activity, ROS accumulation, and biofilm formation of C. albicans were evaluated. The roles of SFU1 in the development, architecture, and spatial distribution of the C. albicans-S. mutans dual-species biofilm were further analyzed. The cariogenic metabolite profile and matrix synthesis were assessed by measuring lactic acid production, lactate dehydrogenase activity, extracellular polysaccharide content, and expression levels of related genes. Results The SFU1 deletion strain exhibited inhibited hyphal formation, reduced metabolic activity, elevated intracellular ROS levels, impaired biofilm formation, and downregulated expression of hyphal and adhesion-related genes ( ALS3, EFG1, UME6 ). In the cross-kingdom biofilm, the sfu1/sfu1 mutant failed to form hyphal networks, resulting in loose biofilm architecture, reduced biomass, and poor integration of S. mutans . Furthermore, the dual-species biofilm showed significantly decreased lactic acid and EPS production. Co-cultured S. mutans exhibited downregulated expression of EPS synthesis genes ( gtfB/C ) and upregulated expression of EPS degradation genes ( dexA/B ). Conclusion SFU1 modulates hyphal development, redox homeostasis, and biofilm formation in C. albicans , thereby profoundly affecting its pathogenic synergy with S. mutans . SFU1 deletion leads to disrupted architecture and attenuated cariogenic virulence of the dual-species biofilm. This study reveals the potential value of targeting fundamental metabolic pathways in C. albicans to interfere with the cariogenicity of cross-kingdom biofilms, and provides a novel perspective for the prevention and therapy of dental caries.