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Tools for the Epidemiology of AMR Plasmids, One-Health Transmission and Surveillance

Lead Research Organisation: University of Bath
Department Name: Life Sciences

Abstract

Antimicrobial resistance (AMR) is spreading rapidly across the globe, and much of this is driven by autonomous 'elements' of DNA called plasmids, which can common carry AMR genes. The ability of AMR plasmids to transfer independently between bacteria, even of different species, presents a serious challenge for epidemiologists attempting to monitor the prevalence and spread of AMR, because the patterns of transmission of AMR plasmids, and AMR genes, might be distinct from those of the bacteria themselves. There is thus a requirement at the core of One-Health AMR management strategies to tease apart the transmission of strains, plasmids (and even individual AMR genes), to implement effective monitoring and risk assessments. Currently, however, our capacity for to track plasmids is limited due to how quickly they evolve and diversify. This network brings together experts who have made critical contributions to this problem through the development of bioinformatics tools, clinical and non-clinical AMR surveillance, and plasmid biology. The network includes partners from low and middle-income countries and will place an emphasis on training and stakeholder engagement.

Technical Summary

Antimicrobial resistance (AMR) is spreading rapidly across the globe, and much of this is driven by plasmids harbouring AMR genes. The ability of AMR plasmids to transfer independently presents a serious challenge for epidemiologists attempting to monitor the prevalence and spread of AMR using genomics approaches, because the patterns of transmission of AMR plasmids, and AMR genes, might be distinct from those of the host bacteria. There is thus a requirement at the core of One-Health AMR management strategies to tease apart the transmission of strains, plasmids (and even AMR genes carried in transposons), to implement effective monitoring and risk assessments. Currently, however, our capacity for effective plasmid molecular surveillance in both clinical and non-clinical settings is limited due to the diversity and speed of evolutionary change of plasmids. This poses both bioinformatic and conceptual problems, and current plasmid typing schemes lack the resolution to infer transmission links. This network brings together experts who have made critical contributions to this problem through the development of bioinformatics tools, clinical and non-clinical AMR surveillance, and plasmid biology. The network has two key aims:i) design and implement a novel platform (plasmid.watch) that incorporates WGS data from plasmids and their host strains (allowing easy cross-referencing between the two), and ii) identify the optimum rapid plasmid typing methods for surveillance. The network includes partners from LMICs and will place an emphasis on ECR training and stakeholder engagement.

Publications

10 25 50
 
Description Comparing the evolution and virulence of the carbapenem resistant Klebsiella pneumoniae (CRKP) clones and their plasmids in Europe and China
Amount £624,998 (GBP)
Funding ID MR/Y015029/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 11/2024 
End 10/2027
 
Description The role of plasmid fusion in the evolution of pathogenic bacteria
Amount £12,000 (GBP)
Funding ID IEC\NSFC\233104 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2024 
End 03/2026
 
Title Genome sequence database 
Description ~3,500 genomes of Klebsiella and Raoultella species sequenced on Illumina (short read) platform from multiple clinical and non-clinical sources in and around Pavia. ~1,000 metagenomics "plate sweeps" of Klebsiella and Raoultella species sequenced. ~1500 genomes completed on long-read (Nanopore or Pac Bio) platform-> >3000 complete plasmid sequences 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Phylogenetic and AMR analyses ongoing, Work on plasmid diversity and transmission - paper currently under review at Lancet Microbe (preprint here: https://www.biorxiv.org/content/10.1101/2024.01.05.574329v1_ 
 
Title genome sequences E. coli and klebsiella spp 
Description We have generated over 3500 complete genome sequences from 15 Klebsiella species form various ecological sources (clinical and non-clinical) in and around the city of Pavia, Italy. We have generated 1000 'plate sweep' datasets from these samples. we have generated almost 1000 complete hybrid assemblies from these samples by complimenting the short read data with long read data. We have generated over 1000 E. coli sequences and 700 Klebsiella sequences from Thailand. We have over 1000 complete hybrid assemblies (using long read data) providing nearly 4000 plasmid sequences 
Type Of Material Database/Collection of data 
Year Produced 2025 
Provided To Others? No  
Impact A number of emerging collaborations and invited presentations 
URL https://pubmed.ncbi.nlm.nih.gov/36411354/
 
Description Public Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 1 hour lecture in Bath Royal Scientific and Literary Society as part of their public lecture series. Provoked lively and interesting debate. Invitations for presentations to local schools received as a result.
Year(s) Of Engagement Activity 2025