Genomic surveillance of multidrug-resistant Klebsiella in Wales reveals persistent spread of Klebsiella pneumoniae ST307 and adaptive evolution of pOXA-48-like plasmids

Rising rates of multidrug-resistant Klebsiella infections necessitate a comprehensive understanding of the major strains and plasmids driving spread of resistance elements. Here, we analysed 540 clinical, screen and environmental Klebsiella isolates recovered from across Wales between 2007 and 2020 using combined short- and long-read sequencing approaches. We identified resistant clones that have spread within and between hospitals including the high-risk strain sequence type (ST)307, which acquired the bla (OXA-244) carbapenemase gene on a pOXA-48-like plasmid. We found evidence that this strain, which caused an acute outbreak largely centred on a single hospital in 2019, had been circulating undetected across South Wales for several years prior to the outbreak. In addition to clonal transmission, our analyses revealed evidence for substantial plasmid spread, mostly notably involving bla (KPC-2) and bla (OXA-48-like) (including bla (OXA-244)) carbapenemase genes that were found among many species and strain backgrounds. Two thirds (20/30) of the bla (KPC-2) genes were carried on the Tn4401a transposon and associated with IncF plasmids. These were mostly recovered from patients in North Wales, reflecting an outward expansion of the plasmid-driven outbreak of bla (KPC-2)-producing Enterobacteriaceae in North-West England. A total of 92.1 % (105/114) of isolates with a bla (OXA-48-like) carbapenemase carried the gene on a pOXA-48-like plasmid. While this plasmid family is highly conserved, our analyses revealed novel accessory variation including integrations of additional resistance genes. We also identified multiple independent deletions involving the tra gene cluster among pOXA-48-like plasmids in the ST307 outbreak lineage. These resulted in loss of conjugative ability and signal adaptation of the plasmids to carriage by the host strain. Altogether, our study provides, to our knowledge, the first high resolution view of the diversity, transmission and evolutionary dynamics of major resistant clones and plasmids of Klebsiella in Wales, and forms an important basis for ongoing surveillance efforts. This article contains data hosted by Microreact.