Reconstructing the Evolutionary Genomics and Pan-Genome Structure of Klebsiella pneumoniae Causing Neonatal Sepsis in Nigerian Tertiary Hospitals

Klebsiella pneumoniae is the predominant cause of neonatal sepsis in Nigerian tertiary hospitals and demonstrates extraordinary genomic plasticity that enables rapid acquisition of resistance and virulence determinants. This study reconstructed the evolutionary genomics and pan-genome structure of K. pneumoniae causing neonatal sepsis across four geographically dispersed Nigerian tertiary hospitals: Usmanu Danfodiyo University Teaching Hospital (North West), University of Maiduguri Teaching Hospital (North East), Aminu Kano Teaching Hospital (North West), and Niger Delta University Teaching Hospital (South South). A total of 120 K. pneumoniae neonatal bloodstream isolates collected over 36 months underwent whole-genome sequencing using Illumina short-read and Oxford Nanopore long-read platforms. Pan-genome analysis, core genome MLST, plasmid reconstruction, and phylogenetic inference were conducted using established bioinformatics workflows. Core genome phylogeny resolved five major lineages, with ST307 and ST147 collectively comprising 52.5 percent of isolates and representing internationally disseminated high-risk clones. The accessory genome encoded diverse ESBL and carbapenemase genes, with blaNDM-1 located on conjugative IncF plasmids in 41.7 percent of ST307 isolates. Hypervirulence loci including iuc (aerobactin) and rmpA were identified in 18.3 percent of isolates, including strains co-carrying carbapenemase genes. Phylogenetic reconstruction identified inter-hospital transmission events across study sites. These findings provide a comprehensive evolutionary and genomic atlas of neonatal K. pneumoniae in Nigeria and establish a foundation for targeted genomic surveillance. Keywords: Klebsiella pneumoniae, whole-genome sequencing, neonatal sepsis, pan-genome, evolutionary genomics.