Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla NDM
The mobile resistance gene bla encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The bla gene is globally distributed across a variety of Gram-negative bacteria on multiple plasmids, typically located within highly...
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| Vydáno v: | Nature communications Ročník 13; číslo 1; s. 1131 - 13 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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England
Nature Portfolio
01.12.2022
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| ISSN: | 2041-1723 |
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| Abstract | The mobile resistance gene bla
encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The bla
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
to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the bla
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
, which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene's global spread. We estimate that bla
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 bla
, but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between bla
-carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the bla
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. |
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| AbstractList | 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. The mobile resistance gene bla encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The bla 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 to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the bla 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 , which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene's global spread. We estimate that bla 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 bla , but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between bla -carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the bla 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. |
| Author | Wang, Ruobing Chen, Hongbin Wang, Hui Acman, Mislav Wang, Qi Sun, Shijun Balloux, Francois Luhmann, Nina Yin, Yuyao Shaw, Liam P van Dorp, Lucy |
| Author_xml | – sequence: 1 givenname: Mislav orcidid: 0000-0003-2587-2836 surname: Acman fullname: Acman, Mislav email: mislav.acman.17@ucl.ac.uk organization: UCL Genetics Institute, University College London, Gower Street, London, WC1E 6BT, UK. mislav.acman.17@ucl.ac.uk – sequence: 2 givenname: Ruobing surname: Wang fullname: Wang, Ruobing organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 3 givenname: Lucy orcidid: 0000-0002-6211-2310 surname: van Dorp fullname: van Dorp, Lucy organization: UCL Genetics Institute, University College London, Gower Street, London, WC1E 6BT, UK – sequence: 4 givenname: Liam P orcidid: 0000-0001-7332-0820 surname: Shaw fullname: Shaw, Liam P organization: Department of Zoology, University of Oxford, Oxford, OX1 3SZ, UK – sequence: 5 givenname: Qi surname: Wang fullname: Wang, Qi organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 6 givenname: Nina orcidid: 0000-0001-8112-7027 surname: Luhmann fullname: Luhmann, Nina organization: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK – sequence: 7 givenname: Yuyao surname: Yin fullname: Yin, Yuyao organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 8 givenname: Shijun surname: Sun fullname: Sun, Shijun organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 9 givenname: Hongbin surname: Chen fullname: Chen, Hongbin organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 10 givenname: Hui surname: Wang fullname: Wang, Hui organization: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China – sequence: 11 givenname: Francois orcidid: 0000-0003-1978-7715 surname: Balloux fullname: Balloux, Francois organization: UCL Genetics Institute, University College London, Gower Street, London, WC1E 6BT, UK |
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| Snippet | The mobile resistance gene bla
encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial... Gene bla NDM, conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al.... |
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| SubjectTerms | Anti-Bacterial Agents - pharmacology beta-Lactamases - genetics beta-Lactamases - metabolism Carbapenems - pharmacology Interspersed Repetitive Sequences - genetics Microbial Sensitivity Tests Plasmids - genetics |
| Title | Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla NDM |
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