Every year, *Campylobacter jejuni* bacteria cause over 80% of the UK’s foodborne infections, costing the economy £900 million, yet scientists understand far less about how this pathogen makes people sick than they do about rivals like *Salmonella*. This project tackles that knowledge gap. The bacterium lives harmlessly in the guts of chickens—trillions per bird—but as few as 100 bacteria can trigger bloody diarrhoea, fever, and severe illness in humans. The researchers have discovered that many *C. jejuni* strains carry a molecular weapon called the Type VI Secretion System (T6SS), which fires toxin “bullets” to kill competing bacteria. They do not yet know how this weapon works differently in chickens versus humans, or whether disabling it could prevent infection. If the team succeeds in characterising these T6SS effectors and their role in gut colonisation, the work could inform two practical outcomes: new antimicrobials that mimic the toxin mechanisms, and vaccine targets derived from the effector proteins. Both would directly address the growing problem of antibiotic resistance in *Campylobacter* infections, which disproportionately harms young children in low-resource settings.
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Campylobacter is the leading cause of foodborne diseases annually in the UK, costing the country's economy a significant amount of money each year. Specifically, the Food Standards Agency estimates that Campylobacter infections alone incur a hefty £900 million expense, out of a total of £1.5 billion for all foodborne infections. Particularly, Campylobacter jejuni species is responsible for over 80% of these cases. This bacterium is becoming increasingly resistant to commonly used antibiotics. Remarkably, it naturally resides in birds, where trillions of these bacteria coexist in their guts without causing harm. However, just 100 of these bacteria can lead to severe illness in humans. Consuming or handling poultry is the main way humans contract the infection, which can result in symptoms like bloody diarrhoea, fever, and abdominal pain. In areas with limited resources, Campylobacter infections are particularly prevalent among young children, leading to health issues such as stunted growth, lifelong physical and cognitive impairments, and in severe cases, death. Despite its prevalence and importance, our understanding of how C. jejuni causes disease is limited when compared to other gut pathogens such as Salmonella. Recently, we have identified many strains of C. jejuni that have a Type VI Secretion System (T6SS). The T6SS acts as a weapon firing bullets (toxins known as effector proteins) that neutralise bacterial competitors, thereby conferring them a competitive edge within a host environment. The functions of C. jejuni T6SS effectors, particularly in chicken and human host environments and their impact on the resulting infection outcome remains unclear. Our research suggests that T6SS and its effectors equip C. jejuni with antibacterial properties to thrive in specific host environments. By analysing the genomes of C. jejuni, we have identified a new range of these effectors and we hypothesise that these are important mediators of C. jejuni pathogenesis and niche establishment. To test this, we propose a multidisciplinary research programme. Our aims and objectives include (1) characterisation of how the T6SS and its effectors of C. jejuni contribute to antibacterial competitive fitness; (2) to determine how different human and chicken in vitro host gut models impact the functionality of the T6SS; and (3) characterise how C. jejuni T6SS and its effectors impact the chicken gut microbial population structure in an in vivo colonisation model. These insights hold transformative potential, informing the development of new antimicrobials based on T6SS toxin mechanisms and novel vaccine targets derived from characterised effectors. The increasing prevalence of Campylobacter infections, coupled with the growing challenge of antimicrobial resistance, presents a significant strain on public health resources, demanding urgent action. To address this pressing issue, our cutting-edge, interdisciplinary project aims to unravel the complex molecular and cellular mechanisms underlying C. jejuni T6SS and effector functions in different hosts, directly aligning with a key BBSRC objective, understanding the rules of life. The knowledge accrued by our research will improve our understanding of this important human pathogen and how it causes disease, with the goal of developing evidence-based interventions to prevent and treat infections and thus improve health. Our impact aligns closely with key pillars of the BBSRC; sustainable agriculture and food, integrated understanding of health and tackling infections.
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