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

ABSTRACT Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hv Kp ) 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 hv Kp 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 bl a NDM-1/5 (lineage 6 and 7), and bla OXA-48/232 (lineage 2 and 5). Specifically, plasmids recovered from the United Kingdom and Russia were lineage-specific, with bla NDM-1 present in lineage 6 and bla NDM-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-hv Kp in clinical settings. Further surveillance of these types of conjugative plasmids in clinical Kp is warranted. IMPORTANCE In this study, we found that the conjugative virulence plasmids containing carbapenem resistance genes could be conjugated to Klebsiella strains, enabling them to express antibiotic resistance and hypervirulence-associated phenotypes simultaneously. More importantly, we observed that the global dissemination of this type of multidrug resistance and hypervirulence conjugative plasmid is lineage specific. The UMAP projection revealed that the regional variations were correlated with ST types and serotypes, which poses a global threat of the CR-hv Kp infection worldwide.