Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis

Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs.

This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees.