KleTy: integrated typing scheme for core genome and plasmids reveals repeated emergence of multi-drug resistant epidemic lineages in Klebsiella worldwide.

Background: Clinically important lineages in Klebsiella, especially those expressing multi-drug resistance (MDR), pose severe threats to public health worldwide. They arose from the co-evolution of the vertically inherited core genome and horizontal gene transfers by plasmids, which has not been systematically explored.

Methods: We designed KleTy, which consists of dedicated typing schemes for both the core genome and plasmids in Klebsiella. We compared the performance of KleTy with many state-of-the-art pipelines using both simulated and real data.

Results: Employing KleTy, we genotyped 33,272 Klebsiella genomes, categorizing them into 1773 distinct populations and predicting the presence of 87,410 plasmids from 837 clusters (PCs). Notably, Klebsiella is the center of the plasmid-exchange network within Enterobacteriaceae. Our results associated the international emergence of prevalent Klebsiella populations with only four carbapenem-resistance (CR) PCs, two hypervirulent PCs, and two hvCR-PCs encoding both carbapenemase and hypervirulence. Furthermore, we observed the ongoing international emergence of bla_NDM, accompanied by the replacement of the previously dominant population, bla_KPC-encoding HC1360_8 (CC258), during 2003-2018, with the emerging bla_NDM-encoding HC1360_3 (CC147) thereafter. Additionally, expansions of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKP) were evidenced in both populations, driven by plasmids of MDR-hypervirulence convergences.

Conclusions: The study illuminates how the global genetic landscape of Klebsiella has been shaped by the co-evolution of both the core genome and the plasmids, underscoring the importance of surveillance and control of the dissemination of plasmids for curtailing the emergence of hvCRKPs.