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

• Published in: Journal of antimicrobial chemotherapy Vol. 74; no. 5; pp. 1218 - 1222
• Main Authors: Lam, Margaret M C, Wyres, Kelly L, Wick, Ryan R, Judd, Louise M, Fostervold, Aasmund, Holt, Kathryn E, Löhr, Iren Høyland
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2019
• Subjects: Anti-Bacterial Agents - pharmacology; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections - microbiology; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - pathogenicity; Microbial Sensitivity Tests; Norway; Original Research; Phylogeny; Plasmids - genetics; Virulence - genetics; Virulence Factors - genetics; Whole Genome Sequencing; Norway
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkz028

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. 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. The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing. 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. 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.