Host-pathogen interactions important in the movement of Campylobacter jejuni from the broiler chicken gut to edible tissues (CampAttack)

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Campattack technical summary
Key tenets of sustainable chicken production are that the animals' health and welfare should be protected and that the end products should not endanger public health. Worldwide most (>75%) chickens are Campylobacter-positive at point of sale, mainly with C. jejuni, and it is estimated that 80% of human cases (~500000) in the UK are chicken-associated. Most UK chickens are grown using intensive systems (broiler production), which can compromise bird welfare and raise the Campylobacter public health threat. There is increasing evidence that edible tissues of chicken, particularly liver, are C. jejuni-positive. Our preliminary data show that infection of liver tissues is a consequence of colonisation of the upper gut with strains of C. jejuni that are inherently better able to leave this organ. Host inflammatory responses, the levels of which are C. jejuni strain-dependent, also play an important role. Building on a strong novel dataset, which has identified a suite of C. jejuni genes and host innate immune responses involved in extra-intestinal spread, our proposed studies will determine the major processes underlying this important bird and public health scenario.
We and our industrial partner Merck Animal Health will conduct in vitro experiments, using novel chicken epithelial cell lines, and infect commercial chickens (Ross 308) in in vivo experiments with wild type C. jejuni and strains with mutations in some of the genes that we have identified as being of high importance. We will also use birds inherently deficient in key immune processes. A range of host immune responses will be measured in all experiments. The identification of the most important pathogen mechanisms and host immune responses involved in the extra-intestinal spread of C. jejuni will inform breeding programmes and immunity-based controls. We will use modelling to investigate the relative importance of the underlying biological mechanisms.

This proposed research will generate new knowledge with the specific aim of enabling the broiler industry to develop better interventions for reducing the problems posed by widespread C. jejuni infection. Specifically, it is intended to provide data to inform our industry partners in developing potential new vaccines and/or chicken breeds resistant to the most damaging and dangerous C. jejuni strains. Industry relevance is underscored by the level of support and involvement - we have three major companies involved in the production chain as active partners. Alongside poultry and allied industry stakeholders, other potential beneficiaries include policymakers in agriculture and food safety, who will benefit from the availability of better control measures, and the public, who will be better protected.
Sustainable production of safe chicken is an international priority and good bird health and welfare are key components of this. It is estimated that global chicken production will have to quadruple over the next ~20 years to satisfy rising demand. However, with around 75% of chickens on sale in the UK Campylobacter-positive, mainly with C. jejuni and a well-established body of research to show that this bacterium is an important endemic chicken pathogen affecting bird health and therefore performance (particularly in rapid-growing breeds), the industry's sustainability is jeopardised.
Contaminated chicken presents two human-health threats. Surface contamination levels can be very high and this can pose a cross-contamination risk during catering. Of greater importance is contamination of deep muscle and liver tissues, reported in up to 27% and 60% of samples respectively. Many epidemiological investigations worldwide have shown that the greater public health risk is from contaminated tissues, where the bacteria are better protected from heat during cooking and under-cooked meat and liver are major infection vehicles. Campylobacter inside undercooked meat and liver will also be better protected from gastric acidity. Broiler producers need to better protect birds from Campylobacter infection but this is very difficult to achieve at present, particularly in summer, as the industry does not have the tools to do so. Of perhaps greater importance for the immediate future is to develop strategies and interventions for confining Campylobacter, principally C. jejuni, to the chicken gut, thus lowering the public health risk from contaminated muscle and liver tissues.
Building on our recent BBSRC-funded work showing that C. jejuni found in UK broiler chicken production form a diverse population in terms of in vivo behaviour in broilers and impacts on bird and public health, our focus will be on those strains that are able to colonise the upper chicken gut and from there spread to edible tissues. We seek to lessen the public health and bird-health threats associated with extra-intestinal spread of C. jejuni. It is likely that our work will also help to lower levels in the broiler intestine.
By addressing a major public-health threat, the interventions that will be developed from our findings have potential to reduce the estimated 700000 cases of infection in the UK annually (with around 100 deaths, mainly in elderly people). The economic benefit of reducing the estimated £1 billion plus annual cost of chicken-associated Campylobacter infection to the UK economy will be allied to financial benefits for the broiler industry that will flow from any intervention to address a cause of reduced bird performance. Moreover, the poultry-industry supply sector will see economic benefits through bringing to market products associated with these interventions, for which demand will be global and will increase as populations grow and developing nations intensify their broiler production. Finally, bird welfare will be improved, a worthwhile outcome in its own right and of particular importance in a society that places high value on animal welfare.