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Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer.


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 blaIMP-4 evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the blaIMP-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 blaIMP-4 to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, blaIMP-4 persisted through diversification of genetic settings that resulted from transfer of blaIMP-4 plasmids between bacterial hosts and of the integron carrying blaIMP-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.

SUBMITTER: Macesic N 

PROVIDER: S-EPMC10409761 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer.

Macesic Nenad N   Hawkey Jane J   Vezina Ben B   Wisniewski Jessica A JA   Cottingham Hugh H   Blakeway Luke V LV   Harshegyi Taylor T   Pragastis Katherine K   Badoordeen Gnei Zweena GZ   Dennison Amanda A   Spelman Denis W DW   Jenney Adam W J AWJ   Peleg Anton Y AY  

Nature communications 20230808 1


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<sub>IMP-4</sub> evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the bla<sub>IMP-4</sub> gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed h  ...[more]

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