Multiomic Analysis of Candida albicans Adaptation during Commensal Coexistence with Staphylococcus aureus

Candida albicans (C. albicans) is a conditionally pathogenic fungus in humans, with its virulence significantly modulated by alterations in the composition of commensal bacteria and the surrounding microecological environment, particularly during cohabitation with methicillin-resistant Staphylococcus aureus (MRSA). Despite this, the molecular mechanisms underlying these interactions remain inadequately elucidated. In this study, we utilized an integrative multiomics approach, including proteomics and proteomics of post-translational modifications (PTMs), to systematically examine the impact of MRSA on protein expression and PTM patterns in C. albicans. Our findings indicate that the presence of MRSA markedly influenced the expression of virulence-associated proteins and modified the phosphorylation and acetylation levels of key proteins involved in essential signaling and metabolic pathways. These modifications were predominantly associated with biological processes such as energy metabolism, metabolic reprogramming, and stress response. Functional enrichment analyses further indicated that these PTMs may play crucial roles in regulating the pathogenicity and environmental adaptability of C. albicans. Moreover, in vitro enzyme activity assays revealed that lysine acetylation induced by MRSA modulated the activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and homoisocitrate dehydrogenase (HIcDH). This suggests that such modifications are involved in the metabolic adaptation and functional reprogramming of C. albicans. In conclusion, this study provides novel insights into the regulation of fungal physiology mediated by MRSA through PTMs, thereby offering a new theoretical framework for understanding fungal pathogenesis and for the development of enhanced anti-infective strategies within the context of bacterial–fungal interactions.