‘Designer probiotics’ may ambush gut pathogens
Scientists from the University of Adelaide in Australia have developed bacteria that have sites on the surface which mimic receptors found on the surface of cells in the host's intestine. Many bacteria, including those responsible for major gut infections, such as cholera, produce toxins, which damage human tissues by binding to receptors in the intestine.
However, during an infection caused by a toxin-producing bacterium, these ‘receptor-mimic probiotics’ could bind the toxins in the gut, thereby preventing the toxins from interacting with receptors on host intestinal cells and causing disease.
The project’s progress is being presented today by Professor James Paton at the Society for General Microbiology's meeting at Heriot-Watt University, Edinburgh.
In an email correspondence with NutraIngredients, Prof Paton said that gut infections with toxigenic bacteria are generally self-limiting, and the body’s natural antibody responses can help to clear the infection within a week or so.
“The toxin-binding probiotics will prevent any toxin-induced disease during this period,” he explained. “Thus, although they don't necessarily prevent infection, they will prevent the disease.
“Having said that, you can also target receptor-mimic probiotics at the adhesions expressed by pathogens, such that you block them from attaching to the gut epithelium. This would prevent the infection altogether.
“An important feature of both approaches is that the pathogen will not be able to evolve resistance to the receptor mimic construct without compromising its capacity to infect humans and cause disease anyway,” he added.
According to the FAO/WHO, probiotics are defined as "live microorganisms which when administered in adequate amounts confer a health benefit on the host".
From E. coli to cholera
“We initially developed this technology to prevent disease caused by strains of E. coli bacteria that produce Shiga toxin. These include the infamous E. coli O157 strain, which causes outbreaks of severe bloody diarrhoea and the potentially fatal haemolytic uraemic syndrome,” said Prof Paton.
“Our prototype receptor mimic probiotic provided 100 per cent protection against otherwise fatal E. coli disease in an animal model.”
“Obviously, we can't test these in human challenge models, and would need to do clinical trials relying on natural infection with the pathogen,” stressed Prof Paton.
The Adelaide-based researcher went on to explain that his group has also developed similar receptor mimic probiotics that are capable of preventing cholera and travellers' diarrhoea.
“As well as being able to treat disease, these probiotics could be given to vulnerable populations following natural disasters to help prevent outbreaks of diseases like cholera,” he said.
From medicine to food
Prof Paton said that, in the first instance, the use of such bacterial strains would be under medical supervision, “there is no reason why they could not be formulated in foods”.
“Indeed, it may be possible to engineer food-grade bacteria such as Lactobacilli and Lactococci to express such receptor mimics,” he added.
Current approaches are limited to a 'harmless strain' of E. coli, like derivatives of E. coli K-12, said Prof Paton. “These strains were subjected to extensive human safety trials in the early 1980s,” he added.
No commercial relationships in place at this stage, added Prof Paton.
Source: Society for General Microbiology Autumn Meeting
Tuesday 8 September
“Recombinant bacteria expressing oligosaccharide receptor mimics: designer probiotics for prevention of enteric infections”
Authors: A.W. Paton, R. Morona, J.C. Paton
