Genomic epidemiology of Neisseria gonorrhoeae in ghana reveals a diverse recombinant pathogen population driven by plasmid acquired and mutational resistance

Neisseria gonorrhoeae is a major sexually transmitted pathogen and an escalating public health threat due to its rapid acquisition of antimicrobial resistance (AMR). Despite a high estimated burden of gonorrhea in Africa, genomic surveillance data from West Africa remain scarce. Establishing localized, evidence-based genomic baselines is vital to appropriately inform national treatment guidelines, improve antimicrobial stewardship, and support public health intervention programs. We analyzed 56 publicly available N. gonorrhoeae genome assemblies originating from Ghana (Accra: N = 39, Takoradi: N = 17; collected 2012–2019). Variant calling was performed against the standard reference genome FA1090 to generate core genome single nucleotide polymorphism (SNP) alignments. Multilocus sequence typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST), and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) schemes were used for lineage classification. Assemblies were screened for acquired genes and chromosomal point mutations to resolve a genotype-based resistome. Population structure was assessed using principal component analysis (PCA), genetic differentiation using sliding-window fixation index (F ST ), and recombination kinetics using linkage disequilibrium (LD) decay. Genomic characterization resolved substantial genetic diversity with multiple co-circulating clades and a complete lack of geographic structuring. High-resolution lineage classification resolved major sequence types, including ST-14,422, ST-1927, and ST-11,210. Predicted plasmid-mediated resistance determinants bla TEM and tet(M) were highly prevalent at 89.3% and 87.5% overall, while key predicted ciprofloxacin resistance-conferring point mutations gyrA_S91F and parC_S87R were present in 87.5% and 12.5% of isolates, respectively. After Bonferroni correction, no resistance determinant showed a statistically significant city-level difference, indicating no robust evidence that unequal city-level sample sizes biased the comparative prevalence analysis. Temporal analysis showed that gyrA_S91F reached 100% prevalence among isolates collected in 2018–2019. Statistical testing revealed that ST-1927 functioned as a clonal reservoir for efflux-mediated resistance, with 100.0% of its isolates carrying the mtrR_A-53del promoter deletion ( p < 0.0001). Genome-wide patterns of sliding-window nucleotide diversity (π), rapid LD decay (r 2 <0.2 within 10 kb), and consistently low windowed F ST (F ST <0.1) supported a highly recombinant, weakly differentiated population. N. gonorrhoeae in Ghana comprises a diverse, highly recombinant population with a pervasive and largely shared resistome across major urban centers. Lineage-specific expansion of mutational resistance and the temporal fixation of ciprofloxacin resistance highlight the risk of emerging resistant strains. These findings establish a crucial genomic baseline for West Africa, providing localized, research-based evidence to support the expansion of ongoing genomic-AMR surveillance and national stewardship efforts.