Predictive modelling to optimise phage intervention against Campylobacter in poultry

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.

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.

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