Deciphering The Molecular Basis of Environmental Persistence in Campylobacter Using a Systems Approach

Campylobacter jejuni is a bacterium that causes food poisoning in people. They usually catch the disease after eating poultry that has not been cooked properly, in which some bacteria survive. In the UK there are around 50,000 reported cases of gastroenteritis caused by Campylobacter each year - but many more cases go unreported because most people recover naturally after a few days. Even so, disease caused by Campylobacter costs the UK economy an estimated £500million. Surprisingly, the bacteria thrive in the guts of poultry, without causing any disease. The control of disease caused by Campylobacter is likely to require several interlinked control measures, including reducing carriage in poultry flocks, cleaning and decontaminating carcasses as they pass through the food chain and encouraging the appropriate cooking of poultry. It has been shown that most of the poultry on sale in the UK is contaminated with Campylobacter. Therefore, in this proposal we focus on ways of controlling carcass contamination. We have already found that some Campylobacter cells are able to resist killing by antibacterial chemicals, limiting the effectiveness of decontamination methods. In this project we will investigate how Campylobacter cells resist killing, how we might use antibacterial chemicals in more effective ways and how we might change some farming practices to limit carcass contamination.

Campylobacter jejuni (Cj) remains a leading cause of food borne infection in the UK with most cases arising from the ingestion of contaminated poultry. Cj is notoriously fastidious and survives poorly under laboratory conditions, yet it appears to be ubiquitous in the environment, forming reservoirs of infection. In addition, it is clear that the bacterium can tolerate abiotic stresses encountered during food processing. Recently, we have shown that this remarkable ability of Cj to survive unfavourable conditions is underlined by the formation of metabolically inactive cells (persister cells) that are analogous to the spores of Gram-positive pathogens. Once conditions improve, these persister cells switch back to a normal-growth state and re-establish a colony and potential subsequent infection. Thus, a full understanding and control of food borne infection mediated by Cj would require an understanding of the formation and regulation of the persister cell phenotype. We will undertake an integrated analysis of persister cell formation and its molecular basis in Cj by combining our expertise in experimental characterisation of pathogenic bacteria and in evolutionary theoretical analysis of bacterial behaviour at network level. This integrated, system-level approach will identify the molecular basis and evolution of persistence in Cj. Ultimately, this will enable us to design novel approaches towards reducing Cj levels in the food chain and that are based on knowledge of the behaviour of the persister population in this bacteria.

Campylobacter is the most common cause of food poisoning in the UK. In 2008 it was responsible for over 300,000 reported cases (England and Wales), resulting in over 15,000 hospitalisations and 76 deaths. Clearly, this has serious health consequences and considerable economic cost - estimated as £583M in 2008. In the UK most cases of C. jejuni infection arise from the ingestion of contaminated poultry. We seek to understand how this bacterium is able to survive in the environment, and in particular during stresses encountered through food processing. This tolerance of abiotic stress is a key reason why food contamination occurs, and we have established that this may in large part be due to the formation of metabolically inactive cells (persister cells) that are analogous to the spores of Gram-positive pathogens. These persister cells may serve as an environmental reservoir and a source of infection, and we intend to provide key information regarding the formation and regulation of the persister cell phenotype, contributing significantly to a full understanding of C. jejuni infection which is likely to lead to effective control of this serious pathogen. Ultimately, this will enable us to design novel approaches towards reducing C. jejuni levels in the food chain - based on knowledge of the behaviour of the persister population in this bacteria. Consequently, we expect that the work will be of considerable interest to four key stakeholder groups, namely representatives from the farming community, meat processors, retailers and government regulatory bodies. We intend to primarily focus our impact activities on the key goal identified in this call, namely to engage and collaborate with industrial partners across the food supply chain, to meet the objective that the outputs of the research are translated to maximum benefit. We have prepared our Pathways to Impact activities so that key stakeholder groups are engaged throughout the project and we will ensure that any potential improvements to the control of Campylobacter within the food supply chain are disseminated effectively and rapidly. We are confident that our science will lead to tangible and relevant advice which will support the reduction of the prevalence of C. jejuni in the food chain.