Novel interventions for eliminating one- health mobile antimicrobial resistance genes from human and animal microbiomes

Lead Research Organisation: University of Oxford
Department Name: Biology

Abstract

Antibiotic resistant bacteria pose a fundamental threat to human health. There is growing recognition that the genes that make bacteria resistant to antibiotics (AMR genes) are transferred between bacteria from agricultural animals and bacteria associated with humans. This exchange of AMR genes is mediated by self-replicating DNA molecules called plasmids that have the ability to transfer between bacterial cells. In this project we will test the ability of specialised viruses that target the plasmid transfer machinery to limit the spread of AMR genes in isolated pathogen populations and complex bacterial communities. Ultimately, this project will lead to the development of new phage based approaches for eradicating AMR genes from humans and agricultural animals that act as important sources of AMR genes, particularly in LMIC settings.

Technical Summary

The most important cases of one-health antimicrobial resistance are caused by the rapid spread of plasmids carrying AMR genes between bacterial strains and species. In this project, we will test the of plasmid-dependent lytic bacteriophages (PDB) to selectively decontaminate bacterial communities by killing AMR plasmid-containing bacteria and by preventing the transfer of AMR plasmids to commensal and pathogen strains. First we will test the impact of key variables on the efficacy of PDB therapy (antibiotic treatment, bacterial diversity, phage mono culture or cocktail) using an established PDB-host system. We will then (i) screen an established collection of phages from agricultural sources to discover new PDBs that have activity against a broader range of one-health AMR plasmids and (ii) test the impact of the aforementioned key variables on the efficacy of these phage in vitro.

Publications

10 25 50
 
Description Interview for BBC article on antibiotic resistance 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview for BBC article on antibiotic resistance and gut microbiome. Quoted in article that featured on BBC homepage.
Year(s) Of Engagement Activity 2023
URL https://www.bbc.com/future/article/20230825-do-antibiotics-really-wipe-out-your-gut-bacteria
 
Description Interview for with farming magazine (Feed Strategy) about antimicrobial use in agriculture 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Interview with journalist from Feed Strategy magazine about use of antibiotics in agriculture, especially as animal growth promoters.
Year(s) Of Engagement Activity 2023
 
Description Interview with DeSmog 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview with DeSmog about recent research work on the use of antibiotics in agriculture.
Year(s) Of Engagement Activity 2023
 
Description Interview with Front Line Genomics 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interview with Frontline Genomics on genomic challenges related to AMR ahead of London Festival of Genomics and Biodata.
Year(s) Of Engagement Activity 2023
URL https://frontlinegenomics.com/the-big-challenge-craig-maclean/
 
Description Interview with The Pathologist 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interview with The Pathologist website about recent research paper on antibiotic use in agriculture
Year(s) Of Engagement Activity 2023
URL https://thepathologist.com/subspecialties/colistin-colist-out
 
Description Oxford University News - Reducing evolution hinders ability to combat resistance 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Oxford university website highlighted recent research on evolutionary mechanisms stabilizing mobile colistin resistance as a news story.
Year(s) Of Engagement Activity 2023
URL https://www.ox.ac.uk/news/2023-10-06-new-research-finds-reducing-antibiotic-usage-animal-feed-not-en...
 
Description Presentation for CABI one-health seminar on One-Health Perspectives to AMR 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a talk on evolutionary perspectives to understanding one-health AMR in a webinar presented by CABI. The webinar will subsequently be made freely available as part of a library on one-health AMR.
Year(s) Of Engagement Activity 2023
URL https://www.cabidigitallibrary.org/product/1k
 
Description Press release to support publication of paper on drivers of antibiotic resistance during infection 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Released press release to support publication of paper entitled "Mixed strain pathogen populations
accelerate the evolution of antibioticresistance in patients". This led to request for for further information from The Economist, a request for an interview with Polish TV and the press release was picked up by a number of digital science media sites.
Year(s) Of Engagement Activity 2023
URL https://www.ox.ac.uk/news/2023-07-12-study-reveals-new-mechanism-rapid-evolution-multi-drug-resistan...