Three Plasmid Strategies, One Intermediate Convergence State: Lineage-Specific Resistance, Virulence Architecture in Dominant Indian Carbapenem-Resistant Klebsiella pneumoniae Clones

Kulkarni, S. M.; Jacob, J. J.; Rajendra, S.; S, P.; T, M. P.; Velmurugan, A.; Nelson, R.; Neeravi, A.; Balaji, L.; Gunasekaran, K.; Manesh, A.; Rajni, E.; Walia, K.; Veeraraghavan, B.

doi:10.64898/2026.06.23.734134

bioRxiv · 10.64898/2026.06.23.734134

Three Plasmid Strategies, One Intermediate Convergence State: Lineage-Specific Resistance, Virulence Architecture in Dominant Indian Carbapenem-Resistant Klebsiella pneumoniae Clones

Kulkarni, S. M.·Jacob, J. J.·Rajendra, S.·S, P.·T, M. P.·Velmurugan, A.·Nelson, R.·Neeravi, A.·Balaji, L.·Gunasekaran, K.·Manesh, A.·Rajni, E.·Walia, K.·Veeraraghavan, B.

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Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a critical global healthcare threat driven by high-risk multidrug-resistant (MDR) clones that acquire hypervirulence genes. Although resistance-virulence co-occurrence is extensively documented, the plasmid-level mechanisms facilitating this convergence remain unclear. In this study, we utilized hybrid short- and long-read whole-genome sequencing of 376 clinical CRKp strains to define the evolutionary trajectories and structural plasmid dynamics of three predominant high-risk clones: ST147 (n=157), ST231 (n=108), and ST2096 (n=111). Carbapenemase genes were present in 90% of isolates, predominantly blaOXA-48-like and blaNDM-5 co-harbored with blaCTX-M-15. Virulence profiling indicated high aerobactin (iuc) prevalence (62.7%), while salmochelin and colibactin were undetected. Hypermucoviscosity occurred infrequently (6.6%) and was independent of rmpA/rmpA2, confirming a clear genotype-phenotype discordance. Comparative plasmid mapping revealed three distinct, lineage-specific plasmid configurations underlying this intermediate convergent pathotype: ST147 exhibited dynamic, mosaic hybrid IncFIB-IncHI1B plasmids; ST2096 showed structurally stabilized hybrids; and ST231 retained virulence and resistance determinants on separate, segregated plasmids. These findings show that convergence is regulated by multiple, clone-specific evolutionary routes rather than a single path, highlighting the critical need for more in-depth genomic surveillance capable of identifying convergent plasmids along with high-risk lineages

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Kulkarni, S. M., Jacob, J. J., Rajendra, S., S, P., T, M. P., Velmurugan, A., Nelson, R., Neeravi, A., Balaji, L., Gunasekaran, K., Manesh, A., Rajni, E., Walia, K., Veeraraghavan, B.. 2026-06-24. Three Plasmid Strategies, One Intermediate Convergence State: Lineage-Specific Resistance, Virulence Architecture in Dominant Indian Carbapenem-Resistant Klebsiella pneumoniae Clones. https://doi.org/10.64898/2026.06.23.734134

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