The impact of Host restriction of Escherichia coli on Transmission dynamics and spread of antimicrobial Resistance

Lead Research Organisation: University of Surrey
Department Name: Veterinary Medicine & Science

Abstract

The occurrence of antimicrobial resistance (AMR) is rapidly increasing worldwide, including in bacteria found in healthy human and animal populations. The recent reports of colistin resistance, potentially associated with colistin usage in agriculture, further raise fears of infections that have become untreatable due to AMR. The commensal flora of humans and animals is a reservoir of AMR genes and Escherichia coli which is part of the healthy micro-flora can carry multiple AMR determinants. Antimicrobial resistance transmission within E. coli appears to be dominated by certain genetic types of the organism. However, to what extent these are restricted to certain host species (animals/humans etc.) is unknown. Such host restriction may be an important determinant of the likelihood of transmission of resistant E. coli between different reservoirs, such as between animal and human hosts. The identification of genes that allow disentanglement of the different modes of AMR transmission is crucial for a more targeted design of controls to prevent and reduce transmission of AMR. The proposed research aims to identify genes of host restriction of E. coli and their potential association with AMR transmission and occurrence. We propose to utilise whole genome sequencing of a large collection of E. coli isolates from human, animal and environmental sources in different geographic areas across Europe and in Vietnam, experimental models to study the role of host restriction determinants in transmission and bacterial fitness, and mathematical modelling. The research aims to produce a risk-assessment, estimating the contribution of different transmission routes and predicting the effect of controls on AMR. The consortium is uniquely placed to perform this research as it consists of experts in the field of microbiology and antimicrobial resistance, who work in human and animal health domains, and represent highly complementary disciplines.

Technical Summary

The prevalence of antimicrobial resistance (AMR) is rapidly increasing worldwide, including in bacteria colonising healthy human and animal populations. The recent reports of plasmid mediated colistin resistance, potentially associated with colistin usage in agriculture, further raise fears of infections that have become untreatable due to AMR. The commensal flora of humans and animals is a reservoir of AMR encoding genes and Escherichia coli in particular can carry multiple AMR determinants. Antimicrobial resistance transmission within E. coli appears to be dominated by certain lineages. However, to what extent these are restricted to certain host species is unknown. Such host restriction may be an important determinant of the likelihood of transmission of resistant E. coli between different reservoirs, such as between animal and human hosts. The identification of determinants that allow disentanglement of the different modes of resistance transmission (i.e. bacteria vs mobile genetic elements such as plasmids) is crucial for a more targeted design of interventions to prevent and reduce transmission of resistance. The proposed research aims to identify determinants of host restriction of E. coli
and their potential association with antimicrobial resistance transmission and prevalence. We propose a One Health approach using mixed methods, including whole genome sequencing of a large collection of E. coli isolates from human, animal and environmental sources in different geographic areas across Europe and in Vietnam, experimental models to study the role of host restriction determinants in transmission and bacterial fitness, and mathematical modelling. The research aims to produce a risk-assessment, estimating the contribution of different transmission routes and predicting the effect of interventions on a single route on the overall prevalence in the different compartments. The consortium is uniquely placed to perform this research.

Planned Impact

It is widely accepted that human and animal pathogens are a growing challenge in health systems in the UK and abroad. Unfortunately, both science and industry have fallen behind in the effort to understand and provide solutions to some of the associated issues. Therefore, our main beneficiaries at this stage will be those in the academic community however, we have described below a number of additional activities that will disseminate our findings to a wider audience and where relevant, have described the potential economic and societal impacts. The outputs of this research will have a range of applications in biotechnology and the medical, and veterinary scientific communities. The results of this work will have an impact on, public health and the development of knowledge for wealth creation.

HECTOR builds a unique One Health consortium across four European countries and introduces one Asian country. It includes academic and public health institutes each contributing essential expertise from varying contexts, thus providing all elements required to study the key research questions addressed in the JPI-AMR Transmission call. In particular, HECTOR enables analysis of an un-precedented strain collection that facilitates the study of transmission of bacterial strains and antimicrobial resistance determinants in their natural host reservoir as well as in different hosts, from healthy and disease states, from different environments and from different continents.

HECTOR enables the academic beneficiaries to expand their expertise in novel approaches towards analysis combining veterinary and human health contexts. In addition, it provides a unique opportunity to verify results of bioinformatics analyses using experimental studies in relevant hosts and to combine these data into mathematical modelling approaches that may result in opportunities for risk assessment. Ultimately, HECTOR will aid in the design of interventions that are evidence based and that target those transmission routes and modes of AMR, that are contributing substantially to transmission of AMR between humans and animals. Thus, the trans-national collaboration proposed for HECTOR will facilitate formation of a consortium that is capable of effectively addressing this due to its highly complementary constituents.

The outputs of the research proposed here will be of great benefit to policy makers such as Defra, FSA and EFSA. In addition it will be of great benefit to the scientific community. Commercial concerns will also benefit from the data generated as it may facilitate the development of novel intervention strategies.

Much of the data generated from the project will be made publicly available, further the PI and CI have strong links with other research groups, Defra, FSA, EFSA and commerce and thus will ensure information is appropriately communicated. We bring together leading experts to create and validate such models, and expect the medium to long-term impact will be felt beyond academics in the AMR field, for example by:

Industry - Defining the mechanisms of AMR transmission and persistence will facilitate the rational design of intervention strategies and products. Predictions arising from this work will be scrutinised for IP.

Policy makers - Improved strategies are required to control AMR in food-producing animals (pigs and chickens in particular). Work leading up to this proposal has already identified some of the key factors involved in AMR transmission and this data has been used as an epidemiological tool. Unravelling the factors influencing AMR transmission in E. coli will aid the effective targeting of resources and policy.

Food producers & consumers - By aiding the rational design of strategies to control AMR in food-producing animals this project will enhance animal and human health, and welfare. Therefore potential exists to improve economic & societal prosperity.

Publications

10 25 50
 
Description Chair of the Humanimal Trust
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Chair of the Veterinary Pathology SAC for the RCPath
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Member of the FSA ACSMF committee
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description NHS AMR Diagnostics committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact The committee provides guidance on the most appropriate diagnostics for use in the NHS and for surveillance.
 
Description Participation in FSA ACSMF AMR committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Participation in FSA ACSMF AMR committee
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
 
Description Royal College of Nursing - Pets for Therapy
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description 2nd Round of OHEJP funding
Amount € 91,000,000 (EUR)
Funding ID NA 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2020 
End 12/2022
 
Description H2020 EJP CO-FUND
Amount € 91,000,000 (EUR)
Funding ID NA 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 01/2018 
End 12/2022
 
Description Low-cost Portable Molecular Diagnostic Platform for Rapid Detection of Poultry Infectious Pathogens (LMDP)
Amount £623,604 (GBP)
Funding ID BB/R012695/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Myanmar Pig Partnership Project Expansion
Amount £359,515 (GBP)
Funding ID BB/S013784/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2019 
End 12/2020
 
Title Chicken, horse and pig gut models 
Description An in vitro model of the chicken, horse and pig intestine has been develop to study AMR transmission (to date only the horse model has been published). 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2019 
Provided To Others? Yes  
Impact Used to study AMR transmission and has already resulted in a reduction in in vivo studies. 
 
Description AiGHD Netherlands 
Organisation Amsterdam Medical Center
Country Netherlands 
Sector Hospitals 
PI Contribution Part of the JPIAMP consortium
Collaborator Contribution Part of the JPIAMP consortium
Impact NA
Start Year 2018
 
Description FLI 
Organisation Friedrich Loeffler Institute
Country Germany 
Sector Academic/University 
PI Contribution Part of the JPIAMP consortium
Collaborator Contribution Part of the JPIAMP consortium
Impact NA
Start Year 2018
 
Description FU - Berlin 
Organisation Free University of Berlin
Country Germany 
Sector Academic/University 
PI Contribution Part of the JPIAMP consortium
Collaborator Contribution Part of the JPIAMP consortium
Impact NA
Start Year 2018
 
Description UCM Spain 
Organisation Complutense University of Madrid
Country Spain 
Sector Academic/University 
PI Contribution Part of JPIAMR consortium
Collaborator Contribution Part of JPIAMR consortium
Impact NA
Start Year 2018
 
Description University of Oxford 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Working together on the sequencing of a panel of E. coli isolates from the project.
Collaborator Contribution Collection and sequencing of E. coli isolates
Impact NA
Start Year 2018
 
Description A poster at the OHEJP conference - The survival of 17 E. coli strains within an in vitro model of the chicken caecal 
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 Poster at OHEJP conference.
Year(s) Of Engagement Activity 2020
URL https://onehealthejp.eu/annual-scientific-meeting-2020/
 
Description AMR MOOC 
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 AMR MOOC for Vets
Year(s) Of Engagement Activity 2020
 
Description AMR Talk WOHC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact AMR talk at the 2020 WOHC
Year(s) Of Engagement Activity 2020
 
Description AVS - Jan 2019 - AMR and biofilms - RVC -UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact A talk on AMR for the Association of Veterinary Students.
Year(s) Of Engagement Activity 2019
 
Description Livestock farming: bacterial zoonotic infections and antimicrobial usage and resistance in Mekong Delta province 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Livestock farming: bacterial zoonotic infections and antimicrobial usage and resistance in Mekong Delta province.
Year(s) Of Engagement Activity 2020
 
Description MEVMAS conference - Rapid diagnostics in animal health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on rapid diagnostics and AMR at MEVMAS conference.
Year(s) Of Engagement Activity 2021
 
Description Med-Vet-Net Association Conference 
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 Organisation of the Med-Vet-Net Association scientific conference - Aimed at brining medics and Vets together to discuss One-Health issues. The 2017 meeting focused on emerging threats and AMR.
Year(s) Of Engagement Activity 2017
 
Description OBN alternatives to antimicrobial talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact OBN alternatives to antimicrobial talk
Year(s) Of Engagement Activity 2020
 
Description Organised microbiology Society Emerging Threats and AMR meeting 
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 Organised a Microbiology Society Surrey meeting on Emerging Threats and AMR.
Year(s) Of Engagement Activity 2018
 
Description Particiation in RSTMH annual meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented a 35 talk on One Health and AMR at the RSTMH annual meeting.
Year(s) Of Engagement Activity 2018
 
Description Poster at Microbiology Society conference - In-vitro Chicken Caecal Model: A Model System to Study the Transfer of ESBL Genes Between E. coli 
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 Poster at the Microbiology society conference - In-vitro Chicken Caecal Model: A Model System to Study the Transfer of ESBL Genes Between E. coli
Year(s) Of Engagement Activity 2019
 
Description Poster presentation at the EJP ASM 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at EJP ASM
Year(s) Of Engagement Activity 2019
 
Description Presentation at St George's hospital June 2018 - One health, Zoonoses and AMR 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation at St George's hospital June 2018 - One health, Zoonoses and AMR
Year(s) Of Engagement Activity 2018
 
Description Talk for the ODN 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Talk on the alternatives to antibiotics for use in animals.
Year(s) Of Engagement Activity 2020
 
Description Talk for the RCGP on AMR a veterinary perspective 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A talk on AMR for the RCGP's
Year(s) Of Engagement Activity 2018
 
Description Talk on the microbiome and AMR - European College of Veterinary Microbiology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on microbiomes and AMR at the European College of Veterinary Microbiology Annual Conference.
Year(s) Of Engagement Activity 2019
 
Description WOHC - Use of big data and digital transformation in microbiology and pathology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Use of big data and digital transformation in microbiology and pathology.
Year(s) Of Engagement Activity 2020