Abstract
Klebsiella pneumoniae is a Gram-negative, facultatively anaerobic member of the Enterobacteriaceae that functions both as a gut commensal and a major opportunistic pathogen implicated in severe hospital and community-acquired infections. The rapid global expansion of antimicrobial-resistant K. pneumoniae lineages, particularly ESBL- and carbapenemase-producing strains, poses an escalating public health threat by eroding available treatment options. This study investigated the genomic architecture and resistance mechanisms of K. pneumoniae isolates recovered from urinary tract infections, wound infections, and cervical cancer cases across Ghana, Togo, and Benin. Eight isolates were subjected to antimicrobial susceptibility profiling and whole genome sequencing using the Illumina MiSeq platform after DNA extraction via the Zymo protocol. Comprehensive genomic analyses including MLST, resistance gene detection (Abricate), phylogenetic reconstruction (iTOL), genomic island prediction (IslandViewer), genome structural analysis (Proksee), and statistical interrogation in R (v4.4.0) were performed to characterize genetic diversity and identify determinants of antimicrobial resistance. The isolates exhibited heterogeneous but overlapping resistance profiles, extensive carriage of AMR genes, and the presence of multiple genomic islands enriched for integrases, transposases, and antibiotic resistance cassettes. MLST and SNP-based comparisons revealed both clonal clusters and genetically divergent lineages, while recombination analysis indicated mutation-driven evolution with lineage-specific recombination hotspots. Conserved gene orientation patterns and regions of atypical GC content further suggested historical acquisition of mobile genetic elements, including plasmid integrations and resistance islands. Collectively, these findings demonstrate the high genomic plasticity, multidrug-resistant phenotypes, and dynamic evolutionary processes shaping K. pneumoniae populations circulating in West Africa. The study underscores the urgent need for continuous regional genomic surveillance to guide treatment policies and limit the further dissemination of high-risk AMR clones.