Convergence and global epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus.

Background : Klebsiella pneumoniae (Kp) is an important pathogen of humans and animals, and recent reports of 'convergent' strains that carry both virulence and antimicrobial resistance genes (ARGs) have raised serious public health concern. The plasmid-borne iuc locus, encoding the siderophore aerobactin, is a key virulence factor in this species. The variant iuc 3 is associated with porcine and human clinical isolates and is carried by mostly uncharacterised IncF plasmids. Methods : We used a combination of short-read and long-read sequencing to characterise IncFIB(K)/IncFII iuc 3-carrying plasmids harboured by 79 Kp isolates and one K. oxytoca isolate recovered as part of two large 'One-Health' studies in Italy (SpARK) and Thailand (OH-DART). Adding data from public repositories gave a combined dataset of 517 iuc 3 isolates, and the plasmids were analysed using both clustering and phylogenetic methods. Findings : We note seven large, convergent, plasmids from Thailand that have emerged through the hybridisation of co-circulating plasmids harbouring iuc 3 and antimicrobial resistance genes (ARGs) encoding extended-spectrum beta-lactamases (ESBLs). We were also able to identify putative parental plasmids which were mostly associated with two neighbouring meat markets, as were the hybrid plasmids. Clustering and global phylogenetic analyses resolved an iuc 3 plasmid sub-group circulating throughout Asia, with occasional examples in Europe and elsewhere. This variant carries multiple ARGs and is commonly harboured by clinical isolates, thus warranting targeted plasmid surveillance. Interpretation : Our study reveals that plasmid hybridisation leading to the convergence of resistance and virulence traits may be very common, even in non-clinical ('One-Health') settings. Population-scale plasmid genomics makes it possible to identify putative parental plasmids, which will help to identify plasmid types that are most likely to hybridise, and what the selective consequences may be for the plasmid and host. A distinct iuc 3 plasmid sub-variant is associated with clinical isolates in Asia which requires close monitoring. ### Competing Interest Statement The authors have declared no competing interest.