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.