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 bla IMP-4 evolution in a hospital using sequence data from 270 clinical...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39915-2 |
| _version_ | 1797558239760482304 |
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| author | Nenad Macesic Jane Hawkey Ben Vezina Jessica A. Wisniewski Hugh Cottingham Luke V. Blakeway Taylor Harshegyi Katherine Pragastis Gnei Zweena Badoordeen Amanda Dennison Denis W. Spelman Adam W. J. Jenney Anton Y. Peleg |
| author_facet | Nenad Macesic Jane Hawkey Ben Vezina Jessica A. Wisniewski Hugh Cottingham Luke V. Blakeway Taylor Harshegyi Katherine Pragastis Gnei Zweena Badoordeen Amanda Dennison Denis W. Spelman Adam W. J. Jenney Anton Y. Peleg |
| author_sort | Nenad Macesic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:27:31Z |
| format | Article |
| id | doaj.art-85869f653dc24df6bcd7067f96605c72 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:27:31Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-85869f653dc24df6bcd7067f96605c722023-11-20T10:07:10ZengNature PortfolioNature Communications2041-17232023-08-0114111210.1038/s41467-023-39915-2Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transferNenad Macesic0Jane Hawkey1Ben Vezina2Jessica A. Wisniewski3Hugh Cottingham4Luke V. Blakeway5Taylor Harshegyi6Katherine Pragastis7Gnei Zweena Badoordeen8Amanda Dennison9Denis W. Spelman10Adam W. J. Jenney11Anton Y. Peleg12Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityMicrobiology Unit, Alfred HospitalDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityDepartment of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash UniversityAbstract 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.https://doi.org/10.1038/s41467-023-39915-2 |
| spellingShingle | Nenad Macesic Jane Hawkey Ben Vezina Jessica A. Wisniewski Hugh Cottingham Luke V. Blakeway Taylor Harshegyi Katherine Pragastis Gnei Zweena Badoordeen Amanda Dennison Denis W. Spelman Adam W. J. Jenney Anton Y. Peleg Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer Nature Communications |
| title | Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer |
| title_full | Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer |
| title_fullStr | Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer |
| title_full_unstemmed | Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer |
| title_short | Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer |
| title_sort | genomic dissection of endemic carbapenem resistance reveals metallo beta lactamase dissemination through clonal plasmid and integron transfer |
| url | https://doi.org/10.1038/s41467-023-39915-2 |
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