Rapid dominance of a carbapenemase-encoding plasmid in clinical Enterobacteriaceae isolates and hypervirulent Klebsiella pneumoniae in Singapore

The dissemination of carbapenemase-encoding plasmids (CP) by horizontal gene transfer in multidrug-resistant bacteria is the major driver for rising carbapenem-resistance. Yet the conjugative mechanics and evolution of clinically relevant plasmids is poorly understood. Based on whole-genome analysis of 1,215 clinical Enterobacteriaceae isolates which resulted in 1,126 CPs with plasmids assignment, we identified the emergence of pKPC2 as dominant CP in Singapore over 5 years, overtaking an earlier dominant plasmid pNDM1. pKPC2 conjugates with high frequency to many Enterobacteriaceae species and hypervirulent K. pneumoniae (hvKp) strains. It is maintained stably without selection pressure in vitro with minimal adaptive sequence changes. Furthermore, capsule and decreasing taxonomic relatedness between donor and recipient pairs are more significant conjugation barriers for pNDM1 than pKPC2. The low fitness costs pKPC2 exerts in Enterobacteriaceae species indicate previously undetected carriage selection in other ecological settings. Contrary to the current paradigm, the ease of conjugation and stability of pKPC2 in hvKp could fuel spread into the community.