Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15.

Margaret MC Lam; Kelly L Wyres; Ryan R Wick; Louise M Judd; Aasmund Fostervold; Kathryn E Holt ORCID logo; Iren Høyland Löhr; (2019) Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15. The Journal of antimicrobial chemotherapy, 74 (5). pp. 1218-1222. ISSN 0305-7453 DOI: 10.1093/jac/dkz028
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BACKGROUND: MDR and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options. OBJECTIVES: Our aim was to characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15. METHODS: The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing. RESULTS: Both isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc) fused with sequences typical of IncFIIK conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene blaCTX-M-15 and seven other AMR genes (blaTEM, aac3'-IIa, dfrA1, satA2, blaSHV, sul1 and aadA1). The other carried remnants of these elements encoding blaTEM and aac3'-IIa, and blaCTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania. CONCLUSIONS: The presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.


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