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

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Acman, Mislav, Wang, Ruobing, van Dorp, Lucy, Shaw, Liam P., Wang, Qi, Luhmann, Nina, Yin, Yuyao, Sun, Shijun, Chen, Hongbin, Wang, Hui and Balloux, Francois (2022) Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla NDM. Nature Communications, 13 (1). 1131. doi:10.1038/s41467-022-28819-2

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Official URL: https://doi.org/10.1038/s41467-022-28819-2

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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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Mobile genetic elements, Antibiotics, Gram-negative bacteria -- Genetics
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 3 March 2022
Dates:
DateEvent
3 March 2022Published
14 February 2022Accepted
Volume: 13
Number: 1
Article Number: 1131
DOI: 10.1038/s41467-022-28819-2
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
PhD scholarshipUniversity College, Londonhttp://viaf.org/viaf/3497159337565813150000
32141001[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81625014[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
MR/P007597/1 Newton Fundhttp://dx.doi.org/10.13039/100010897
81661138006Newton Fundhttp://dx.doi.org/10.13039/100010897
ISSF3Wellcome Trusthttp://dx.doi.org/10.13039/100010269
19RX03Wellcome Trusthttp://dx.doi.org/10.13039/100010269
GCRF scheme[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDUniversity College London Hospitals NHS Foundation Trusthttp://dx.doi.org/10.13039/501100008721
Excellence Fellowship University College, Londonhttp://viaf.org/viaf/3497159337565813150000
BB/R01356X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
220422/Z/20/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269

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