Role of the mobilome in the global dissemination of the carbapenem resistance gene blaNDM

Abstract

The mobile resistance gene blaNDM encodes the NDM enzyme capable of hydrolysing carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. blaNDM is globally distributed across a variety of Gram-negative bacteria and is typically located within a transposon-rich genomic region common to multiple plasmids. We compiled a dataset of over 2000 bacterial genomes harbouring the blaNDM gene including 112 new PacBio hybrid assemblies from China and developed a novel computational approach to track structural variants in bacterial genomes. We were able to correlate specific structural variants with plasmid backbones, bacterial host species and sampling locations, and identified multiple transposition events that occurred during the global dissemination of blaNDM. Our results highlight the importance of transposons in the global spread of antimicrobial resistance genes and suggest that genetic recombination, rather than mutation, was the dominant force driving the evolution of the blaNDM genomic region.