Contribution of Horizontal Gene Transfer Networks to the Co-Evolution of Virulence and Resistance in Uropathogenic Escherichia coli Across Nigerian Clinical and Environmental Reservoirs

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections globally, and the co-evolution of virulence and antimicrobial resistance within UPEC populations through horizontal gene transfer (HGT) represents a complex and clinically significant evolutionary process. The extent and nature of HGT networks enabling virulence-resistance co-evolution in UPEC strains circulating across Nigerian clinical and environmental reservoirs remain uncharacterized. This study applied comprehensive comparative genomics and HGT network analysis to 200 UPEC isolates from clinical UTI cases, environmental water samples, and poultry fecal sources collected across the North Central (Benue State), South East (Abia State), and South West (Osun State) geopolitical zones of Nigeria. Hybrid whole-genome sequencing using Illumina and Nanopore platforms resolved plasmid architectures and chromosomal mobile genetic elements. Virulence gene profiles (papGII, hlyA, cnf1, sat, iucA) and resistance determinants were comprehensively identified. HGT network construction used co-occurrence analysis of shared mobile genetic elements across isolates. Bayesian ancestral state reconstruction traced co-evolutionary trajectories of virulence and resistance gene acquisition. Results revealed that 43 percent of isolates harbored virulence-resistance co-carrying plasmids, a significantly higher rate than reported in European studies. HGT network analysis identified a densely connected hub of IncF plasmids facilitating bi-directional gene exchange between clinical UPEC and poultry E. coli. Ancestral reconstruction showed that virulence gene acquisition preceded resistance gene incorporation in 68 percent of traced evolutionary trajectories. This study constitutes an original evolutionary genomics contribution to UPEC biology in the Nigerian One Health context. Keywords: uropathogenic E. coli, horizontal gene transfer, virulence-resistance co-evolution, comparative genomics, One Health.