Convergence of virulence and multidrug resistance in a single plasmid vector in multidrug-resistant Klebsiella pneumoniae ST15

Abstract

These authors contributed equally to this work # Corresponding author: iren.hoyland.lohr@sus.no SYNOPSIS: Background: Multidrug resistance (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: 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 IncFII K conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene bla CTX-M-15 and eight other AMR genes (bla TEM , dfrA1, satA2, bla SHV , sul1, aadA1) . The other carried remnants of these elements encoding bla TEM and aac3'-IIa, and bla CTX-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.

A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307

“…Other virulence determinants were uncommon and played no dominant role in the examined KpSC population. However, as previously reported by Lam et al, virulence-encoding genes were found in convergence with blaCTX-M-15 on mosaic plasmids in two ST15 isolates 32 .…”

“…(Genbank accession CP073783-CP073787) ESBL isolate showed blaCTX-M-15 to be situated on an IncFII plasmid without any of the virulence loci. However, two ST15 ESBL isolates (BioSample accession SAMEA5063299, SAMEA5063230), harboured the iuc and rmpA2 virulence loci, as well as blaCTX-M-15 on the same mosaic plasmid, as described by Lam et al 32 .…”

Phylogenomics of globally spread Clonal Groups 14 and 15 of Klebsiella pneumoniae

“…Though our sample is clearly dominated by genomes from European countries, CG14 and CG15 subclades seem to be globally distributed (11,32), similarly to other subclades within CG147, CG258, CG307 or CG101. This suggests their specialisation through acquisition of adaptive traits that seem to favour colonisation, spread and persistence in shifting conditions (7)(8)(9)(10).…”

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

“…This is consistent with their local dissemination or recent acquisition from a common source, a finding supported by the discovery of four novel but similar iuc3 encoding plasmids in these isolates. Of greatest concern was the detection of at least nine distinct convergence events between AMR and hypervirulence (encompassing 7·3% of isolates) plus seven novel dual AMR + iuc containing plasmids, increasing the total number of convergent plasmids reported so far by almost 50% [49,[80][81][82][83]. Given that our isolate collection represented a snapshot from seven diagnostic laboratories, we predict that many additional convergent plasmid variants await future identification.…”