Predictive modelling to optimise phage intervention against Campylobacter in poultry
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Biosciences
Abstract
Campylobacter jejuni and C. coli are bacteria that cause are human food-borne infections through out the world. In common with other European countries, campylobacters are the most commonly recorded cause of acute bacterial enteritis in the UK with 57,772 cases of campylobacteriosis reported to the Health Protection Agency in 2009. However, due to under-reporting the true incidence could be 8-fold higher with estimated costs to the UK economy approaching £600 million per annum. Birds in general naturally carry the bacteria but it is poultry that act as a major vehicle for the infection of the humans through undercooked meat or cross-contamination of other foods in the kitchen. This project will investigate use bacteriophage as a sustainable form of biocontrol against Camplyobacter colonizing and contaminating poultry and poultry meat. Bacteriophage, often simply called phage, are viruses that kill bacteria. Phage are quite specific, they will only affect the target bacteria and not other bacterial flora. They are also common in the environment such that all people encounter them on a daily basis, which includes their presence on fresh produce. The application of phages to kill campylobacters on chickens therefore represents a natural and sustainable measure to reduce the numbers of the pathogen entering the food chain from this source. The optimal use of phage therapy will require good understanding of phage-Campylobacter interactions at all stages of poultry farming and processing. This proposal will build a comprehensive understanding of Campylobacter-bacteriophage interactions in poultry from colonization of the birds to presentation of the meat at retail. It will combine laboratory work and predictive modelling to design protocols for optimal practical phage therapy.
Technical Summary
The use of bacteriophage targeted against Camplyobacter infection in poultry is a potentially powerful form of biocontrol. Optimal use of phage therapy will require good understanding of phage-Campylobacter interactions at all stages of poultry farming and processing. This proposal will build a uniquely comprehensive understanding of Campylobacter-bacteriophage interactions in poultry from infection to carcass. It will combine laboratory interventions and predictive modelling in three strands. We will: 1. Build a comprehensive understanding of in vivo phage-Campylobacter kinetics in broiler chickens. 2. Determine how post-slaughter kinetics contributes to phage therapy efficacy. 3. Use our predictive models to design protocols for optimal practical phage therapy.
Planned Impact
The current proposal is in response to the BBSRC, Defra and FSA research call in support of policy makers and industry to achieve a reduction in the levels of Campylobacter entering the food chain and thereby the incidence of foodborne Campylobacter enteritis in the UK population. Campylobacters are the most commonly recorded cause of acute bacterial enteritis in the UK with an estimated cost approaching £600 million per annum to the economy. Poultry are a major source of infection and this proposal represents a sustainable intervention to reduce the levels of Campylobacter in broiler chickens and on chicken meat. Potential Beneficiaries 1. The public will benefit through a reduction in the incidence of campylobacteriosis, and therefore reduced morbidity, general improved health and no loss of earnings through illness. 2. Policymakers will benefit on completion of the project by gaining an understanding of how phage therapy can be applied, any constraints on efficacy and how these may relate regulatory issues that are currently in focus with an increasing number of permissions being sought for the application of phage for therapeutic and biosanitization purposes in agriculture and on ready to eat foods. 3. The poultry industry will benefit through the provision of a sustainable intervention against Campylobacter in poultry 4. Agri-food and healthcare industries in general may benefit on completion of the project through the provision of quantitative mathematical models that will predict the phamakinetics of phage in an intestinal environment and beyond 5. The food industry in general will benefit in the long term through increased consumer confidence if the levels of foodborne illness decline
People |
ORCID iD |
Ian Connerton (Principal Investigator) |
Publications
Adriaenssens EM
(2012)
A suggested new bacteriophage genus: "Viunalikevirus".
in Archives of virology
Aprea G
(2018)
Isolation and morphological characterization of new bacteriophages active against Campylobacter jejuni.
in American Journal Clinical Microbiology & Antimicrobials
Brathwaite KJ
(2013)
Complete Genome Sequence of Universal Bacteriophage Host Strain Campylobacter jejuni subsp. jejuni PT14.
in Genome announcements
Brathwaite KJ
(2015)
Host adaption to the bacteriophage carrier state of Campylobacter jejuni.
in Research in microbiology
Connerton PL
(2011)
Campylobacter bacteriophages and bacteriophage therapy.
in Journal of applied microbiology
Firlieyanti AS
(2016)
Campylobacters and their bacteriophages from chicken liver: The prospect for phage biocontrol.
in International journal of food microbiology
Hobley L
(2020)
Dual Predation by Bacteriophage and Bdellovibrio bacteriovorus Can Eradicate Escherichia coli Prey in Situations where Single Predation Cannot
in Journal of Bacteriology
Hooton SP
(2016)
The Bacteriophage Carrier State of Campylobacter jejuni Features Changes in Host Non-coding RNAs and the Acquisition of New Host-derived CRISPR Spacer Sequences.
in Frontiers in microbiology
Hooton SP
(2014)
Campylobacter jejuni acquire new host-derived CRISPR spacers when in association with bacteriophages harboring a CRISPR-like Cas4 protein.
in Frontiers in microbiology
Description | Campylobacter jejuni and C. coli are bacteria that cause are human food-borne infections throughout the world. Poultry are a major source of infection through undercooked meat or cross-contamination of other foods in the kitchen. We have found ways of delivering naturally occurring viruses that specifically kill the bacteria and only the target bacteria, in poultry and on poultry meat. We have developed novel approach to evaluate risk reduction in food borne pathogen numbers through the application of bacteriophage during food processing. Mathematical models describing the effects of bacteriophage require the inclusion of the non-linear interaction between bacteria and bacteriophage, although these approaches can produce insights into the dynamics of the process, uncertainties in the parameters make the outcomes difficult to estimate.The quality of the fit for many different parameter combinations can be expressed as the likelihood. By repeating the fitting procedure the likelihood functions can be estimated, and by using experimental data to calibrate the model predictions can then be made from the likelihood surfaces. This procedure will not yield a single value for the prediction of the bacterial load after treatment, but a distribution of values, which tells us the chance that a will we find a certain bacterial load. Based on this distribution we can evaluate the reduced risk associated with the treated product. The approach has the potential to provide a tool to allow faster, cheaper validation and cost-benefit analysis of novel bacteriophage interventions and lower the bar to market entry. |
Exploitation Route | Commercial companies are using the models and developing delivery protocols for bacteriophage on poultry meat in non-EU countries. |
Sectors | Agriculture, Food and Drink,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Bacterial infections of man and animals impact directly on human health and food quality. The rise in antibiotic resistance has adversely impacted on our ability to treat these infections. Bacteriophage are naturally occurring viruses that specifically kill target bacteria, and have the potential to be used for therapeutic and food disinfection purposes. We have developed models and application parameters that will assist in the practical application of bacteriophage. |
Sector | Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Development of a Bacteriophage Product to Control Campylobacter Contamination in Kenya |
Amount | £226,681 (GBP) |
Funding ID | BB/P02355X/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2017 |
End | 02/2019 |
Title | Campylobacter jejuni subsp. jejuni PT14, complete genome. |
Description | Genome sequence of universal bacteriophage host strain Campylobacter jejuni subspecies jejuni PT14 |
Type Of Material | Database/Collection of data |
Year Produced | 2012 |
Provided To Others? | No |
Impact | No actual impacts realised to date |
Title | Campylobacter phage CP30A, complete genome. |
Description | Recombination and diversity amongst Campylobacter bacteriophage in chickens. GenBank |
Type Of Material | Database/Collection of data |
Year Produced | 2012 |
Provided To Others? | No |
Impact | No actual impacts realised to date |
Title | Campylobacter phage CP8, complete genome |
Description | Complete DNA sequnence of the Eucampyviriae used in phage therapy applications. NCBI GenBank |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | No |
Impact | No actual impacts realised to date |
Description | Bacteriophage applications in food safety |
Organisation | Experimental Zooprophilactic Institute of Campania and Calabria Italy |
Country | Italy |
Sector | Academic/University |
PI Contribution | Development of methods for application and scale up |
Collaborator Contribution | Animal trial facilities |
Impact | Multi-disciplinary: Microbiology, Quantitative modelling, Veterinary Sciences, Public Health |
Start Year | 2015 |
Description | Modelling pharmakinetics for phage therapy |
Organisation | Paul Ehrlich Institute |
Country | Germany |
Sector | Academic/University |
PI Contribution | Development of model systems to assess Campylobacter phage replication and production of primary kinetic data. |
Collaborator Contribution | Extending our existing models of phage dynamics. |
Impact | At an early stage of the collaboration so no outputs as yet. The collaboration is multidisciplinary with respect to Microbiological data collected in the UK and mathematical approaches adopted in Germany. |
Start Year | 2018 |
Description | Quantitative modelling of phage therapy |
Organisation | Royal Holloway, University of London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Research collaboration |
Start Year | 2013 |
Description | Use of bacteriophage in prepared foods |
Organisation | PTC - Phage Technology Center GmbH |
Country | Germany |
Sector | Private |
PI Contribution | Design of experimental trials. Phage discovery and molecular characterisation. |
Collaborator Contribution | Performing experimental trials. Scale-up of phage production. |
Impact | Phages 2015: Bacteriophage in Medicine, Food and Biotechnology 01-02 September 2015 St Hilda's College, Oxford, UK Investigation of structures influencing bacteriophage infection of Campylobacter jejuni Lukas Lis1, and Ian F Connerton2 1PTC Phage Technology Center GmbH, Im Kompetenzzentrum BioSecurity, Bönen, Germany 2Division of Food Sciences, School of Biosciences, University of Nottingham, Loughborough, Leicestershire, UK |
Start Year | 2013 |
Description | CHRO 2013: A real time model of in-vivo Campylobacter populations within chicken caeca: applications for bacteriophage host dynamics |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Stimulated interest in research activity. Limiting the number of parameters and animals in enteric experiments. |
Year(s) Of Engagement Activity | 2013 |
Description | Cafe Scientifique Event |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Wide ranging discussion. Interest in responses antibiotic resistance from public audience. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.meetup.com/nottingham-culture-cafe-sci/events/calendar/ |
Description | Campylobacter workshop 2013 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Discussion with international representatives. Collaboration |
Year(s) Of Engagement Activity | 2013 |
Description | Public lecture Nottingham: Bacteriophage Control of Bacterial Pathogens: My enemy's enemy is my friend? |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Public interest in phage therapy against antibiotic resistant bacteria. On-line discussions |
Year(s) Of Engagement Activity | 2013 |
Description | Science with Impact - Annual Conference 2015 BSAS & WPSA |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Discussion between a mixed industry and academic audience. To be confirmed. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.bsas.org.uk/events-conferences/annual-conference-2015/ |