Profiling the landscape of carbapenem resistance and hypervirulence in Klebsiella pneumoniae : a global epidemiological analysis of the plasmidome

Abstract

The emergence and spread of carbapenem resistance (CR) and hypervirulence (hv) in Klebsiella pneumoniae represent a growing global health threat. Plasmids play an important role in the dissemination of these traits; however, the plasmidome of draft genomes of a large number of K. pneumoniae has not been analyzed so far. To recover K. pneumoniae plasmids, OMAP-KP was developed, achieving a recall rate of 85.27 % for plasmids exceeding 10,000 bp in length from draft genomes. From a global collection of 69,969 K. pneumoniae genomes, we identified 226,110 plasmids, providing the most comprehensive profiling of the K. pneumoniae plasmidome to date. The study recovered 12,790 KPC-encoding plasmids, 6214 NDM-encoding plasmids, and 6843 hv plasmids. Plasmid KPC PC_392 was found to be associated with ST11 K. pneumoniae in China, featuring the klcA within the genetic context around bla<inf>KPC</inf>. NDM plasmids exhibited a widespread distribution, and stabilization began before 2015. There was an increased prevalence of bla<inf>NDM-5</inf> with the qnrS1 gene compared to bla<inf>NDM-1</inf> after 2020. The frequent convergence of CR and hv plasmid pairs was observed in different STs: hv PC_499 with KPC PC_362 (ST11) and OXA PC_7078 (ST15), and hv PC_394 with OXA PC_7078 (ST2096) and OXA PC_804 (ST383), suggesting clone transmission of K. pneumoniae carrying CR-hv plasmid pairs. Alarmingly, PC_394 can encode both hv loci and CR genes, with an increasing prevalence detected from the public database from North America and Europe & Central Asia after 2019, which might result from the change of isolation or treatment strategy, or potentially from the ongoing spread of plasmids that have not been detected in other areas. This observed pattern coincides with the period of the COVID-19 pandemic needs further investigation. This study highlights the potential to integrate plasmid-level analysis into genome surveillance projects. The plasmidome reference and identification approach can track the emergence and convergence of CR and hv PCs in the evolution and transmission of K. pneumoniae, paving the way for more effective interventions to protect public health.