Food Poisoning Bacteria’s Sugar Coating Could Be Its Undoing

Underreporting and the difficulties presented in establishing causal relationships between illness and food contamination mean that the burden of foodborne disease to public health and the economy is frequently underestimated.

A 2015 report from the World Health Organization on the global burden of foodborne diseases presented the first-ever estimates of disease burden caused by 31 foodborne agents (bacteria, viruses, parasites, toxins and chemicals) at global and regional levels. One of the leading causes of foodborne illness is the bacterium Campylobacter jejuni, highlighting the importance of being able to identify infections caused by this bacterium and reduce its prevalence in the food chain.

To learn how Campylobacter hides from the body’s immune system, why some people are more susceptible than others, and the potential role that carbohydrate-based diagnostics could play in the fight against the bacterium, we spoke to Professor Rob Field, Co-founder of Iceni Diagnostics.

Karen Steward (KS): Can you tell us a bit about the problems that Campylobacter jejuni presents?

Rob Field (RF): Campylobacter is considered to be one of the most common bacterial causes of human gastrointestinal infection in the world, with half a million cases a year in the UK. Often associated with the ingestion of infected food, it is a major cause of food poisoning and traveler’s diarrhea.

Campylobacter has evolved to colonize the gut of the chicken, where it can live happily and does not cause illness or disease in the bird so it is difficult to detect. The problem arises when chicken meat becomes contaminated during slaughter, or through bacteria in chicken livers used for pâté.

Over recent years there has been a rise in infection, however it is often not reported as the symptoms, although severe, are short-lived in an otherwise healthy person and generally do not require medical intervention. The issue is that it can be fatal to some and for others lead to serious complications months later, including reactive arthritis and paralytic diseases such as Guillain-Barre.

There is a need to increase understanding of the pathogen in order to develop a novel way to contain it without the use of antibiotics. Also, to develop a way to identify the pathogen accurately with a simple test that does not require sophisticated laboratory diagnostics, and to create a way to distinguish which patients are likely to have an extreme reaction in order to prioritize medical attention.

To address these issues, Iceni Diagnostics, as developers of carbohydrate-based diagnostics and therapeutics, is partnering with the Quadrum Institute within an EU program called Sweet Crosstalk which is looking at the role of glycoscience in the control of Campylobacter.

Sugars (carbohydrates) have the benefit that they are temperature stable reducing the need for the cold chain and they are also ubiquitous, taking many major metabolic, structural and physical roles in biological systems.

To give an example, 90 % of infections use carbohydrate recognition to bind with targets in human or animal bodies. As the mechanism is specific to each particular strain of pathogen, it can be used to identify the strain of bacteria or virus.

Iceni Diagnostics has already developed a simple dip test that can distinguish between particular strains of flu virus and is looking to use this knowledge to create a diagnostic for Campylobacter.

KS: Why are some people more susceptible to infection with Campylobacter jejuni than others? Are there any steps people can take to reduce their susceptibility?

RF: Identifying why some people are more susceptible to Campylobacter is one of the strands of our research.

Campylobacter is particularly virulent as, once in the human body, the bacteria are able to mimic the sugar structures that coat our own nervous system’s cells to humanise themselves and become invisible to the body’s immune response.

These simple sugar structures are called glycans and are used to identify cells within the body, distinguishing them from those of other species. Glycans are important for signaling within the immune system and for creating barriers to infection.

By mimicking these sugars, Campylobacter can avoid detection thus preventing the body’s defense system from doing its job.

The story is further complicated as the difference between blood groups is also determined by glycans on the cell surface – and this creates variations between individuals within the population.

There is evidence that Campylobacter recognizes sugars that look similar to these blood group antigens. So, where individuals have sugar signatures that are recognized by the Campylobacter, they are more susceptible to infection.

The importance of these sugars has only recently been revealed, so a better understanding of this process will help us to develop a point-of-care diagnostic.

In future this will enable identification of those most at risk of complications.

However, basic food hygiene when cooking or handling raw poultry and ensuring that food is properly cooked is still the best way to avoid infection.

KS: How do you propose to reduce the prevalence of Campylobacter in poultry? As a food animal, might there be issues with regards to food safety that must be taken into consideration when developing a strategy? 

RF: The focus of our research is to investigate alternatives to the use of antibiotics. Increasing natural competition for resources from other bacteria in the gut, perhaps through a probiotic, might be a way to manage the population of Campylobacter and boost the health of poultry.

Intervention strategies focused at the farm level have been shown to be successful in reducing the number of Campylobacter cases in several countries.

Professor Nathalie Juge is Group Leader at the Quadrum Institute and her group is looking at glycobiology of host-microbe interactions in the gut. She comments that Campylobacter can scavenge the sialic acid sugar from the host, so reducing the opportunity for other microorganisms to flourish in the gut. By blocking sialic acid binding by Campylobacter, this is one of the options for an effective anti-infective strategy.

Other research is ongoing into the early pathogen detection on the farm, which could be used to support husbandry practices to prevent spread of the pathogen, as well as processing plant technologies to assess and prevent contamination of food products in abattoirs.

Food safety is of course the highest consideration, but the focus here is on rebalancing nature rather than introducing new elements.

Anna MacDonald (AM): How can sugar chemistry be applied to diagnostics to detect and distinguish between pathogens?

RF: As the carbohydrate mechanism is specific to each particular strain of infection, it can be used to form a sensor for the disease. We have found that by selecting a specific sugar or panel of key sugars, one can distinguish between organisms using their carbohydrate binding properties and this allows identification of the pathogen.

For example, at Iceni Diagnostics we have recently gained a patent for our simple dip-stick test that uses differences between the carbohydrate detectors in the different strains of influenza virus to detect and distinguish between human and avian flu. With a slight modification, the simple test could provide a rapid non-invasive test for equine flu too.

The sensor uses sugars tagged with inexpensive gold nanoparticles; if the virus is present it will stick to the particles, pulling them closer together. This creates a photophysics reaction and the sample changes color. We see easy-to-use tests as a cheap option for rapid screening.

AM: What advantages do these carbohydrate-based diagnostics have over more commonly used protein-based tests?

RF: Carbohydrates are typically much more stable both chemically and biologically than protein-based diagnostics, which require cold storage. Therefore, the comparatively “low technology” approach of carbohydrate-based diagnostics allows greater tolerance of environmental conditions during storage, extending product shelf life.

In many instances, carbohydrates are also cheaper to produce than the antibodies or DNA used in other diagnostic tests. For some pathogens, such as influenza virus, the surface of the virus changes rapidly (and hence the need to change influenza vaccines annually), but the ability of the virus to bind carbohydrate does not change significantly from year to year. So, surface-binding antibodies are expected to have shorter utility than carbohydrates in a diagnostic sense.

Professor Rob Field, co-founder of Iceni Diagnostics was speaking to Dr Karen Steward and Anna MacDonald, Science Writers for Technology Networks.