Pan-African genomics of Pseudomonas aeruginosa highlights regional population structure and AMR stratification

Abstract Background Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial infections and a World Health Organization "Priority 1" critical pathogen. Despite the escalation of global antimicrobial resistance (AMR), the genomic landscape of P. aeruginosa across Africa remains profoundly undermapped, representing less than 5% of global data. Methods We conducted a continent-scale analysis of 467 high-quality assemblies (completeness >95%) spanning 17 African countries over 26 years (1998–2024). We analyzed these publicly available assemblies using standardized annotation, iterative pangenome clustering across seven amino acid identity thresholds (50%–98%), and exploratory core-genome SNP phylogenetics, evaluating regional functional markers via pangenome wide association studies (Pan-GWAS). Results Analysis identified an exceptionally "open" pangenome architecture (γ=0.23) comprising 25,501 gene families within the African P. aeruginosa population. Phylogenomic reconstruction resolved 466 unique core genome SNP profiles characterized by strong regional clustering. Notably, we identify an "African Clonal Inversion," where ST111 (46.5%, 33/71) outnumbers the global "super-clone" ST235 (14.1%, 10/71) among identified high risk clone isolates (n=71) by more than three-fold. The resistome is geographically stratified, with blaNDM-1 dominating Northern/Eastern country subsets and blaVIM-2 concentrated in Southern Africa. Pan-GWAS identified regional accessory gene-presence associations, including Type VI Secretion System (tla3) enrichment in North Africa and phenazine biosynthesis (phzA2) clusters in West Africa. Conclusion These findings, integrated into a live interactive dashboard (Microreact), establish a comprehensive genomic framework for the surveillance of P. aeruginosa in Africa, providing critical insights into the evolution of this pathogen within the global context.