A sweet trick for fighting infection

 

Posted: 16 August 2012


We all know that eating too much sugar is not great for your health. But there’s more to sugars than the granules you sprinkle into coffee. Sugar structures, or carbohydrates, play important roles in how bacteria, fungi and viruses interact with our bodies and cause infection. And Professor Stefan Oscarson is looking at ways to harness those interactions in our favour - whether to design new antibiotics or improve vaccines.

In some cases, sugar molecules on the surface our cells are like hooks or locks that bacteria and viruses can access by binding to them through proteins on their own surfaces. This molecular interaction prevents the pathogens from being washed away by mechanical defence systems and gives them the possibility to start an infection and also to go inside the cells, where they are less visible to our immune system and can cause trouble.

Professor Oscarson, who is Professor of Chemical Biology at UCD, and members of his team at CSCB and UCD School of Chemistry and Chemical Biology are looking at ways to make mimics of the carbohydrate structures in the lab.

“The idea is that if you can identify these receptors and synthesise a mimic of the carbohydrate, that would then bind to a protein on a free bacterium or virus,” he explains. “Then the protein on the pathogen is occupied and it can no longer interact with the receptor on the human cell.”

Blocking the binding of bacteria to cells could potentially offer a route to new antibiotics, which are sorely needed due to the rise in antibiotic-resistant strains of bacteria. One of the pathogens that Professor Oscarson is investigating is E. coli, which can cause urinary tract infections, and his team has identified a carbohydrate-based structure that could potentially block the bacterium from accessing human cells.

Another branch of the lab’s work looks at using carbohydrate chemistry to improve vaccines. “Many recent mass vaccines in Ireland are based on carbohydrate structures that you find on the surface of bacteria,” says Professor Oscarson.

He describes carbohydrate-based vaccines such as the ‘Hib’ vaccine against a strain of meningitis-causing bacteria as a “tremendous success” but notes there could be room to improve further too. In some cases where the native bacterial structure can’t be used a synthetic structure produced in a chemistry lab is an attractive alternative. And it’s not just bacteria he has in his sights: he is also looking at how clever chemistry could combat hard-to-thwart fungal pathogens.

More generally, he has also cracked a major challenge in carbohydrate chemistry - while in Sweden he figured out how to increase the yield of sucrose synthesis. While plants make it apparently effortlessly, making table sugar in the lab was difficult as the yields were low.

But in 2000, Oscarson invented an improved method: “Earlier yields were around 10 per cent, but we managed to get a yield of 80 per cent,” he recalls. “It was the holy grail of carb chemistry.”


Professor Stefan Oscarson from the UCD School of Chemistry and Chemical Biology and Centre for Synthesis and Chemical Biology was interviewed by freelance journalist Dr