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. 2019 May 1;74(5):1218-1222.
doi: 10.1093/jac/dkz028.

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

Margaret M C Lam  1 , Kelly L Wyres  1 , Ryan R Wick  1 , Louise M Judd  1 , Aasmund Fostervold  2   3 , Kathryn E Holt  1   4 , Iren Høyland Löhr  2
Affiliations

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

Margaret M C Lam et al. J Antimicrob Chemother. .

Abstract

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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Figures

Figure 1.
Figure 1.
Map of novel mosaic hv-MDR plasmids, showing regions of homology with closely related AMR (pKp_Goe_579-1) and virulence (pK2044) plasmids, generated using Mauve. The location of known virulence genes (blue), as well as AMR genes and their associated mobile elements (red), and the plasmid replication modules are also indicated.
Figure 2.
Figure 2.
Recombination-free maximum likelihood phylogeny showing virulence and AMR properties of 318 ST15 isolates. Tips are coloured by the country of isolation (for n ≥ 4 genomes) or geographical region as indicated; Norwegian convergent hv-MDR strains KP_NORM_BLD_2014_104014 and KP_NORM_BLD_2015_112126 are labelled as A and B, respectively, and highlighted in a grey box along with the closely related Romanian isolate. Columns are as follows: (i) percentage coverage of the blaCTX-M-15/iuc plasmid pKp104014_1, determined by read mapping; (ii) presence of the aerobactin synthesis locus iuc and the hypermucoidy rmpA2 gene (coloured in black); (iii) yersiniabactin ICEKp variants detected; and (iv) capsule K-locus (KL), followed by AMR determinants as labelled (coloured in black for presence).
See this image and copyright information in PMC

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