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Published on: January 10, 2019
A Broad-Host-Range Plasmid Outbreak: Dynamics of IncL/M Plasmids Transferring Carbapenemase Genes
María Getino1, María López-Díaz2, Nicholas Ellaby2
1Department of Comparative Biomedical Sciences, School of Veterinary Medicine, University of Surrey, Guildford GU2 7AL, UK.
Abstract:
IncL/M broad-host-range conjugative plasmids are involved in the global spread of blaOXA-48 and the emergence of blaNDM-1. The aim of this study was to evaluate the transmission potential of plasmids encoding the emergent NDM-1 carbapenemase compared to the pandemic OXA-48. The conjugation rate and fitness cost of IncM2 and IncL plasmids encoding these carbapenemase genes were tested using a variety of host bacteria. Genomic analysis of uropathogenic Escherichia coli SAP1756 revealed that blaNDM-1 was encoded on an IncM2 plasmid, which also harboured blaTEM-1, bleMBL and sul1 and was highly similar to plasmids isolated from the same geographical area. Conjugation experiments demonstrated that NDM-1 and OXA-48-carrying plasmids transfer successfully between different Enterobacterales species, both in vitro and in vivo. Interestingly, E. coli isolates tested as recipients belonging to phylogroups A, B1, D and F were able to receive IncM2 plasmid pSAP1756, while phylogroups B2, C, E and G were not permissive to its acquisition. In general, the IncL OXA-48-carrying plasmids tested transferred at higher rates than IncM2 harbouring NDM-1 and imposed a lower burden to their host, possibly due to the inactivation of the tir fertility inhibition gene and reflecting their worldwide dissemination. IncM2 plasmids carrying blaNDM-1 are considered emergent threats that need continuous monitoring. In addition to sequencing efforts, phenotypic analysis of conjugation rates and fitness cost are effective methods for estimating the pandemic potential of antimicrobial resistance plasmids.
Insights
Broad-host-range plasmids carrying carbapenemase genes like NDM-1 and OXA-48 spread globally. IncL plasmids with OXA-48 transferred more efficiently than IncM2 plasmids with NDM-1, indicating different pandemic potentials.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Broad-host-range conjugative plasmids, including IncL/M types, are key drivers in the global dissemination of carbapenemase genes.
- The emergence of New Delhi metallo-beta-lactamase 1 (NDM-1) and the pandemic spread of OXA-48-like carbapenemases are significant public health concerns.
Purpose of the Study:
- To compare the transmission potential, conjugation rates, and fitness costs of IncM2 plasmids encoding NDM-1 versus IncL plasmids encoding OXA-48.
- To assess the host range and permissiveness of different bacterial phylogroups to plasmid acquisition.
Main Methods:
- Conjugation experiments were performed in vitro and in vivo using various host bacteria to evaluate plasmid transfer rates.
- Genomic analysis was conducted on uropathogenic Escherichia coli SAP1756 to characterize the plasmid carrying blaNDM-1.
- Fitness costs associated with plasmid carriage were assessed in different bacterial hosts.
Main Results:
- Both NDM-1 (IncM2 plasmid) and OXA-48 (IncL plasmid) carrying plasmids successfully transferred between Enterobacterales species.
- IncL plasmids carrying OXA-48 demonstrated higher transfer rates and lower host fitness burdens compared to IncM2 plasmids carrying NDM-1.
- Specific Escherichia coli phylogroups showed differential permissiveness to IncM2 plasmid acquisition.
Conclusions:
- IncM2 plasmids harboring blaNDM-1 represent emergent threats requiring continuous surveillance.
- Phenotypic analyses of conjugation and fitness are crucial for predicting the pandemic potential of antimicrobial resistance plasmids.
- Understanding plasmid transmission dynamics is vital for controlling the spread of carbapenemase-producing Enterobacterales.
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