Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM

The mobile resistance gene bla_NDM encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The bla_NDM gene is globally distributed across a variety of Gram-negative bacteria on multiple plasmids, typically located within highly recombining and transposon-rich genomic regions, which leads to the dynamics underlying the global dissemination of bla_NDM to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the bla_NDM gene, including 104 newly generated PacBio hybrid assemblies from clinical and livestock-associated isolates across China. We develop a computational approach to track structural variants surrounding bla_NDM, which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene’s global spread. We estimate that bla_NDM emerged on a Tn125 transposon before 1985, but only reached global prevalence around a decade after its first recorded observation in 2005.