Whole-Genome Computational Analysis of Neisseria gonorrhoeae: Antimicrobial Resistance Determinants, Functional Subsystems, and Evolutionary Insights

Neisseria gonorrhoeae remains a major global health threat due to its rapid acquisition of antimicrobial resistance (AMR) and limited therapeutic options. Here, we performed whole-genome computational analyses of ten geographically diverse isolates to unravel resistance determinants, functional subsystem variability, and evolutionary dynamics. Resistome profiling revealed a dual architecture of conserved chromosomal mutations including gyrA, folP, rpoB, and efflux-associated macAB/emrAB-TolC alongside sporadic plasmid-borne genes (blaTEM, tetM), underscoring both stability and heterogeneity in resistance mechanisms. Subsystem categorization demonstrated a conserved backbone in core metabolism and DNA processing, contrasted by variability in protein synthesis, stress response, and virulence pathways. Phylogenomic reconstruction distinguished divergent lineages from Malawi and Australia, while plasmid carriage was not clade-specific, highlighting the role of horizontal gene transfer in shaping population structure. Pangenome and whole-genome alignment analyses revealed a stable core genome complemented by strain-specific unique coding sequences, including virulence factors (factor H-binding protein, Maf toxins, siderophore transporters) and mobile genetic elements, reinforcing the mosaic nature of the gonococcal genome. Collectively, these findings provide high-resolution insights into the resistome and adaptive genome architecture of N. gonorrhoeae, emphasizing the urgent need for integrated genomic surveillance to inform treatment and control strategies against this rapidly evolving pathogen.