Global dissemination of conjugative virulence plasmids co-harboring hypervirulence and multidrug resistance genes in Klebsiella pneumoniae

Abstract

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has led to a high mortality rate in the clinical setting and garnered significant attention in the clinical and scientific communities. It is still not clear which major mechanisms mediate the rapid evolution of hvKp in clinical settings since the plasmid-encoding hypervirulence phenotype is considered non-conjugative. In this study, we revealed a conjugative plasmid, p16HN200-Vir, encoding virulence-associated iuc operon (iucABCDiutA) and resulting in a hypervirulent phenotype. In silico analysis of Kp strains from NCBI predicted a total of 94 p16HN200-Vir-like conjugative virulence plasmids. These sequences were identified in 19 sequence types (STs) of the host with significant geographical variations in distribution across countries and continents. Notably, ST11 was predominant in China, while ST147 and ST395 were prominent in the United Kingdom and Russia, respectively. These plasmids could be categorized into seven lineages, some of which formed distinct geographical clusters in China and the UK, while others exhibited a hybrid population. Importantly, most of the plasmids carried different carbapenemases, including blaNDM-1/5 (lineage 6 and 7), and blaOXA-48/232 (lineage 2 and 5). Specifically, plasmids recovered from the United Kingdom and Russia were lineage-specific, with blaNDM-1 present in lineage 6 and blaNDM-5 in lineage 7. Our data suggest that this type of conjugative plasmids has spread around the world and contributed significantly to the current rapid evolution of CR-hvKp in clinical settings. Further surveillance of these types of conjugative plasmids in clinical Kp is warranted.