Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer
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Hawkey, J
Vezina, B
Wisniewski, JA
Cottingham, H
Blakeway, LV
Harshegyi, T
Pragastis, K
Badoordeen, GZ
Dennison, A
Spelman, DW
Jenney, AWJ
Peleg, AY
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Abstract
Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of bla IMP-4 evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the bla IMP-4 gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of bla IMP-4 to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, bla IMP-4 persisted through diversification of genetic settings that resulted from transfer of bla IMP-4 plasmids between bacterial hosts and of the integron carrying bla IMP-4 between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.
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Nature Communications
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14
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© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Microbiology
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Macesic, N; Hawkey, J; Vezina, B; Wisniewski, JA; Cottingham, H; Blakeway, LV; Harshegyi, T; Pragastis, K; Badoordeen, GZ; Dennison, A; Spelman, DW; Jenney, AWJ; Peleg, AY, Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer, Nature Communications, 2023, 14, pp. 4764