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

Mislav Acman (), Ruobing Wang, Lucy Dorp, Liam P. Shaw, Qi Wang, Nina Luhmann, Yuyao Yin, Shijun Sun, Hongbin Chen, Hui Wang and Francois Balloux
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Mislav Acman: University College London
Ruobing Wang: Peking University People’s Hospital
Lucy Dorp: University College London
Liam P. Shaw: University of Oxford
Qi Wang: Peking University People’s Hospital
Nina Luhmann: Warwick Medical School, University of Warwick
Yuyao Yin: Peking University People’s Hospital
Shijun Sun: Peking University People’s Hospital
Hongbin Chen: Peking University People’s Hospital
Hui Wang: Peking University People’s Hospital
Francois Balloux: University College London

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The mobile resistance gene blaNDM encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The blaNDM 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 blaNDM to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the blaNDM 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 blaNDM, which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene’s global spread. We estimate that blaNDM emerged on a Tn125 transposon before 1985, but only reached global prevalence around a decade after its first recorded observation in 2005. The Tn125 transposon seems to have played an important role in early plasmid-mediated jumps of blaNDM, but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between blaNDM-carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the blaNDM gene was primarily driven by successive between-plasmid transposon jumps, with far more restricted subsequent plasmid exchange, possibly due to adaptation of plasmids to their specific bacterial hosts.

Date: 2022
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DOI: 10.1038/s41467-022-28819-2

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