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

• Published in: Nature communications Vol. 13; no. 1; p. 1131
• Main Authors: Acman, Mislav, Wang, Ruobing, van Dorp, Lucy, Shaw, Liam P., Wang, Qi, Luhmann, Nina, Yin, Yuyao, Sun, Shijun, Chen, Hongbin, Wang, Hui, Balloux, Francois
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.03.2022; Nature Publishing Group
• Subjects: 631/181/735; 631/208/212; 631/326/22/1434; 631/326/41/2530; Antibiotics; Bacteria; Bacterial diseases; Carbapenems; Computer applications; Genomes; Genomics; Gram-negative bacteria; Humanities and Social Sciences; Livestock; multidisciplinary; Plasmids; Science; Science (multidisciplinary); Transposons
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28819-2

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 Tn 125 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 bla NDM , but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between bla NDM -carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the bla NDM 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. Gene bla NDM , conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al. study the dynamics underlying bla NDM dissemination across over 6000 bacterial genomes, and identify mobile genetic elements and specific mobilisation events likely involved in the gene’s global spread.