Highly prevalent plasmid-encoded ter operon enhances the persistence of virulence plasmid and phage resistance in Klebsiella pneumoniae
Plasmids are key drivers of bacterial adaptation through horizontal gene transfer, particularly of virulence determinants. While most virulence plasmids lack conjugation machinery, their rapid dissemination in hypervirulent Klebsiella pneumoniae suggests alternative transmission mechanisms.. Here, we demonstrate that the virulence plasmid pKp2449vir, hijacked conjugation elements from a co-resident plasmid, forming a conjugative co-integrate plasmid (termed pKp2449vir/tra) capable of horizontal transfer to diverse K. pneumoniae (75/101) and Escherichia coli (17/75) strains. Acquisition of pKp2449vir/tra exhibited variable fitness and virulence effects, highlighting the complex interactions between plasmid and their bacterial hosts. Furthermore, most transconjugant exhibited plasmid instability, whereas the plasmid-encoded tellurium resistance operon (ter) conferred a selective advantage for plasmid persistence. The transconjugant Kp85TC displayed enhanced resistance to phage killing, while terC deletion restored bacterial phage susceptibility. Transcriptional analysis revealed that terC deletion altered expression of both plasmid and chromosomal genes, including upregulated ter operon genes and downregulated hok gene, which is responsible for phage resistance. Genomic analyses further linked the ter operon to virulence plasmids in clinical dominant K. pneumoniae lineages (ST11 and ST23). Collectively, these findings elucidate the molecular mechanisms driving virulence plasmid spread and host adaptation, offering critical insights into the evolution of this high-risk pathogen.