Lysine succinylome analysis of MRSA reveals critical roles in energy metabolism and virulence

MRSA's resistance poses a global health challenge. This study investigates lysine succinylation in MRSA using proteomics and bioinformatics approaches to uncover metabolic and virulence mechanisms, with the goal of identifying novel therapeutic targets. Mass spectrometry and bioinformatics analyses mapped the MRSA succinylome, identifying 8 048 succinylation sites on 1 210 proteins. These analyses included Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network construction (e.g. using the STRING database), providing a comprehensive functional and interactive landscape of succinylated proteins. The succinylated proteins were predominantly involved in cytoplasmic metabolic processes, with enrichment in glycolysis/gluconeogenesis and the tricarboxylic acid (TCA) cycle. Both of these pathways are critical for MRSA's energy production, growth, and virulence, supplying the necessary metabolic intermediates and energy to support bacterial survival and pathogenicity. Motif analysis revealed 13 conserved motifs, while PPI analysis highlighted FnbA as a central virulence factor. Succinylation significantly influences MRSA's metabolism and virulence, potentially impacting biofilm by modifying key proteins such as FnbA, bifunctional autolysin, and LuxS. These findings provide new avenues for developing antibiofilm strategies and therapeutic interventions against MRSA.