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. Results: We designed KleTy, which consists of dedicated typing schemes for both the core genome and plasmids in Klebsiella. We demonstrated the superior performance of KleTy over many state-of-the-art pipelines using both simulated and real data. We used both schemes to genotype 33,272 Klebsiella genomes, categorising them into 1,773 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 blaNDM, accompanied by the replacement of the previously dominant population, blaKPC-encoding HC1360_8 (CC258), during 2003-2018, with the emerging blaNDM-encoding HC1360_3 (CC147) thereafter. Additionally, expansions of 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.

The authors have declared no competing interest.

ZZ was supported by the National Natural Science Foundation of China (32170003, 32370099), the Natural Science Foundation of Jiangsu Province (BK20211311), Jiangsu Specially-appointed Professor Project, and the Suzhou Science and Technology Innovations Project in Health Care (SKY2021013). YH was supported by the grants from National Natural Science Foundation of China (32170032, 32370034), National Major Youth Talent Project A, Jiangsu Specially-appointed Professor Project, Suzhou Innovation Leading Talent Project (ZXL2022456), Jiangsu Improvement Project of Science, Technology, and Education (No. CXZX202231). HL was supported by the National Natural Science Foundation of China (No. 82202465). LZ was supported by the Graduate Research and Innovation Projects of Jiangsu Province (KYCX22_3187).

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