Dataset Information

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 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.

SUBMITTER: Macesic N

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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]

PMID: 37553339

Similar Datasets

Project description:Acquisition of metallo-β-lactamases (MBLs) represents one of most relevant resistance mechanisms to all β-lactams, including carbapenems, ceftolozane and available β-lactamase inhibitors, in Pseudomonas spp. VIM-type enzymes are the most common acquired MBLs in Pseudomonas aeruginosa and, to a lesser extent, in other Pseudomonas species. Little is known about the acquisition dynamics of these determinants, that are usually carried on integrons embedded into chromosomal mobile genetic elements. To date, few MBL-encoding plasmids have been described in Pseudomonas spp., and their diversity and role in the dissemination of these MBLs remains largely unknown. Here we report on the genetic features of the VIM-1-encoding plasmid pMOS94 from P. mosselii AM/94, the earliest known VIM-1-producing strain, and of related elements involved in dissemination of MBL. Results of plasmid DNA sequencing showed that pMOS94 had a modular organization, consisting of backbone modules associated with replication, transfer and antibiotic resistance. Plasmid pMOS94, although not typable according to the PBRT scheme, was classifiable either in MOBF11 or MPFT plasmid families. The resistance region included the class I integron In70, carrying bla V IM-1, in turn embedded in a defective Tn402-like transposon. Comparison with pMOS94-like elements led to the identification of a defined plasmid lineage circulating in different Pseudomonas spp. of clinical and environmental origin and spreading different MBL-encoding genes, including bla IMP-63, bla BIM, and bla V IM-type determinants. Genetic analysis revealed that this plasmid lineage likely shared a common ancestor and had evolved through the acquisition and recombination of different mobile elements, including the MBL-encoding transposons. Our findings provide new insights about the genetic diversity of MBL-encoding plasmids circulating among Pseudomonas spp., potentially useful for molecular epidemiology purposes, and revealed the existence and persistence of a successful plasmid lineage over a wide spatio-temporal interval, spanning over five different countries among two continents and over 20-years.

Project description:BackgroundAntibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation.MethodsElectronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments.ResultsWe identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment.ConclusionsThis investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets