Tracking clonal and plasmid transmissions in colistin and carbapenem resistant Klebsiella pneumoniae

Infections caused by multidrug resistant bacteria are a major threat to public health, and their potential transmission events are therefore monitored in hospital settings. In contrast, the surveillance of mobile genetic elements that facilitate the spread of antimicrobial resistance genes have been challenging given their often mosaic composition. In this study, we tracked both clonal and plasmid transmission in colistin and carbapenem-resistant K. pneumoniae (ColR-CRKP) strains using short and long read sequencing technologies. First, we observed three clonal transmissions within two sequence types (ST15 and ST392), all of which contained IncL plasmids as well as the bla_NDM-1 carbapenemase, however, these were not always co-located. We found that one IncL plasmid containing bla_NDM-1 had been transferred between one ST392 cluster and the ST15 cluster, and that the promiscuous IncL plasmid carrying bla_OXA-48 was likely shared between the second ST392 cluster and a singleton of the same ST. The bla_NDM-1 gene of these last isolates was carried on incHI2. We found 0-11 SNP differences within the clonal outbreaks over a timeframe of 15 weeks. Between the plasmids within the clonal transmissions, we found 0-2 SNP differences, and 0-2 SNPs in the transfer within and between clusters and STs, with only an insertion of an additional insB insertion element in ST15. This shows high stability of the plasmids both within clonal transmissions as well as upon transfer to same or different STs. Taken together, despite the fact that IncL as well as bla_NDM-1 were common in this collection, we found a total of four different plasmids and a network of plasmid transfers, which we were only able to track applying both short and long read sequencing. This emphasizes the need to also investigate plasmid-mediated transmission which could be another key epidemiological link and useful for effective containment of outbreaks.