Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of<i>Klebsiella pneumoniae</i>

<jats:title>Abstract</jats:title><jats:p><jats:italic>Klebsiella pneumoniae</jats:italic>(<jats:italic>Kp</jats:italic>) has emerged as an important cause of two distinct public health threats: multidrug resistant (MDR) healthcare-associated infections<jats:sup>1</jats:sup>and community-acquired invasive infections, particularly pyogenic liver abscess<jats:sup>2</jats:sup>. The majority of MDR hospital outbreaks are caused by a subset of<jats:italic>Kp</jats:italic>clones with a high prevalence of acquired antimicrobial resistance (AMR) genes, while the majority of community-acquired invasive infections are caused by ‘hypervirulent’ clones that rarely harbour acquired AMR genes but have high prevalence of key virulence loci<jats:sup>3–5</jats:sup>. Worryingly, the last few years have seen increasing reports of convergence of MDR and the key virulence genes within individual<jats:italic>Kp</jats:italic>strains<jats:sup>6</jats:sup>, but it is not yet clear whether these represent a transient phenomenon or a significant ongoing threat. Here we perform comparative genomic analyses for 28 distinct<jats:italic>Kp</jats:italic>clones, including 6 hypervirulent and 8 MDR, to better understand their evolutionary histories and the risks of convergence. We show that MDR clones are highly diverse with frequent chromosomal recombination and gene content variability that far exceeds that of the hypervirulent clones. Consequently, we predict a much greater risk of virulence gene acquisition by MDR<jats:italic>Kp</jats:italic>clones than of resistance gene acquisition by hypervirulent clones.</jats:p>