Potential role of lysine acetylation in the stepwise adaptation of <i>Candida albicans</i> to fluconazole

<i>Candida albicans</i>, an opportunistic fungal pathogen, presents significant clinical challenges due to its escalating resistance to azole antifungals, especially fluconazole. This study investigates the role of lysine acetylation in the development of azole resistance using multiple strains isolated from a single patient with varying resistance levels. Through advanced proteomic analysis, we identified numerous lysine acetylation sites on proteins involved in key metabolic pathways. The results revealed a dynamic change in the acetylation of proteins related to energy metabolism - specifically, those connecting pyruvate to the tricarboxylic acid cycle-which correlated with the evolution of resistance. Additionally, increased acetylation was observed in proteins linked to ribosome synthesis and translation processes. These findings suggest that lysine acetylation is crucial for regulating metabolic and protein synthesis pathways, potentially influencing azole resistance in <i>C. albicans.</i>