Tracking microevolution events among ST11 carbapenemase-producing hypervirulent Klebsiella pneumoniae outbreak strains

The recent convergence of genetic elements encoding phenotypic carbapenem-resistance and hypervirulence within a single Klebsiella pneumoniae host strain represents a major public concern. To obtain a better understanding of the genetic characteristic of this emerging ‘superbug’, the complete genomes of 3 isolates of ST11 carbapenemase-producing hypervirulent K. pneumoniae were generated using the Oxford nanopore MinION platform. Comparative whole-genome analysis identified 13 SNPs and 3 major regions of indels in the chromosomes of the clonally disseminated isolates. ISKpn18-mediated disruption in the mgrB gene, which was associated with colistin resistance, was identified in two later strains, leading to the emergence of hypervirulent K. pneumoniae that was simultaneously colistin- and carbapenem-resistant. Five plasmids were recovered from each isolate, including a 178 Kb IncHI1B/FIB-type rmpA2-bearing virulence plasmid, a 177.5 Kb IncFII/R self-transferable blaKPC-2-bearing MDR plasmid, a 99.7 Kb Incl1 plasmid and two ColRNAI-type plasmids of sizes of 11.9 and 5.6 Kb, respectively. The presence of homologous regions between the non-conjugative virulence plasmid and conjugative blaKPC-2-bearing MDR plasmid suggests that transmission of the virulence plasmid from ST23 K. pneumoniae to ST11 CRKP may be mediated by the co-integrated transfer of these two plasmids. Emergence of colistin-resistant and carbapenemase-producing hypervirulent K. pneumoniae strains further emphasizes the urgency for the establishment of a coordinated global program to eradicate hypervirulent and/or pan-drug-resistant strains of K. pneumoniae from clinical settings and the community.