Convergence of resistance and virulence traits in iuc3-carrying plasmids in Klebsiella pneumoniae

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. Of the six iuc variants described, iuc1, iuc2a and iuc2b are associated with clinical isolates, whilst iuc3 is more commonly associated with porcine isolates. We have used a combination of short-read and long-read sequencing to characterise IncFIB(K)/IncFII iuc3-carrying plasmids harboured by 80 Kp isolates (and one K. oxytoca isolate) recovered as part of two large 'One-Health' studies, one in Italy (SpARK) and one in Thailand (OH-DART). Additional data was used from the public repositories. Seven of the iuc3 plasmids from Thailand, mostly originating from pork and poultry meat sourced from two neighbouring markets, have acquired ARGs, including ESBLs, through hybridisation between iuc3 plasmids and co-circulating resistance plasmids. By incorporating publicly available data, we carried out clustering and global phylogenetic analyses (n=495) which resolved an iuc3 plasmid sub-group circulating throughout Asia. This variant carries multiple ARGs and is commonly harboured by clinical isolates, thus warranting targeted plasmid surveillance. 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, and that a distinct iuc3 plasmid variant is associated with clinical isolates in Asia.