Network analysis of antimicrobial resistance in Staphylococcus aureus: Characterization of hub genes and their functional implications

Abstract

Staphylococcus aureus is a pathogenic bacterium that is increasingly resistant to antibiotics. To identify genes that facilitate this resistance, we analyzed 1062 genomes from the NCBI Genome database. From these genomes, we compile a list of 229 antimicrobial resistance (AMR) genes from the CARD, ResFinder, MEGARes, and AR-ANNOT databases. We then constructed and analyzed their interaction network using multiple network analysis tools to identify critical central genes, designated as hub genes. Our findings revealed that mecA, fosB, arlR, mepA, mgrA, and arlS held the highest significance in the interaction network, suggesting their roles as key genes in AMR. To further examine these genes, we performed functional enrichment and molecular function analyses to better understand the biological processes these genes impact. Additionally, our results indicate that these central genes are predominantly associated with antibiotic efflux and target replacement. These mechanisms confer resistance to disinfectants, fluoroquinolones, antiseptics, tetracyclines, and β-lactam penicillin. Identifying core genes associated with AMR and characterizing their biological functions provides crucial insight into the potential for developing new therapeutic strategies.