Phylogenomics and Evolutionary Dynamics of Multidrug-Resistant Klebsiella pneumoniae High-Risk Clones Circulating in Nigerian Healthcare Institutions

Multidrug-resistant Klebsiella pneumoniae high-risk clones, particularly those of sequence types ST258, ST147, and ST307, have emerged as dominant global nosocomial pathogens, yet their phylogenomic structure and evolutionary trajectory within Nigerian healthcare institutions have never been characterised through comprehensive whole genome analysis. This dissertation conducts a phylogenomic investigation of multidrug-resistant Klebsiella pneumoniae high-risk clones across six Nigerian healthcare institutions, spanning Lagos (South West), Kano (North West), Enugu (South East), Jos (North Central), Maiduguri (North East), and Port Harcourt (South South). A total of 180 Klebsiella pneumoniae isolates collected over three years were whole-genome sequenced using Illumina and Oxford Nanopore platforms. Multilocus sequence typing, resistome analysis, plasmid replicon typing, and core genome phylogenetic analysis were performed using Kleborate, Prokka, and IQ-TREE. Three dominant high-risk clones were identified: ST147-KL64 (35 percent), ST307-KL102 (24 percent), and ST258-KL107 (18 percent). NDM-1 carbapenemase carriage was predominant in ST147, while OXA-48-like producers dominated in ST258. Bayesian phylogenetic dating estimated ST147 introduction into Nigerian hospitals approximately 8 years before sampling, followed by clonal expansion facilitated by blaKPC-2-encoding IncFIB plasmids. Inter-facility transmission was confirmed by maximum parsimony analysis of closely related core genome SNP clusters. The dissertation constitutes the first phylogenomic atlas of K. pneumoniae high-risk clones in Nigeria and provides a molecular epidemiology foundation for targeted infection control intervention. Keywords: Klebsiella pneumoniae, phylogenomics, high-risk clones, carbapenem resistance, Nigeria