Copycat chemistry disarms bugs

Researchers develop protein copies which make bacteria impotent.

Concerns in hospitals about bacterial resistance to current antibiotic treatments continue to rise and global research teams are racing to develop new antibiotics to outwit the pathogens. Now an international team of researchers has approached the problem from a new angle, finding a way to make bacteria impotent by preventing them from binding to cell surfaces.

Many pathogens, including bacteria, bind to host cell surfaces through branched, complex carbohydrate structures on glycoproteins. In a bid to disarm bacteria, the researchers, led by Ben Davis at the University of Oxford, UK, decided to construct copies of these structures. They focused on glycodendrimers, which mimic the branched carbohydrates on glycoproteins. To make copies of glycoproteins, Davis and coworkers then attached glycodendrimers to a protein to form a new class of compounds which they labelled glycodendriproteins.

Bacteria stick to cell surfaces using adhesins, which often form from sugar-binding proteins called lectins. The team claims that its glycodendriproteins attach to lectin adhesins on bacteria and selectively degrade them. ’This leaves the bug without a method of binding to the host and so leaves it ’’handless’’’ explains Davis. ’Very early observations suggest that the treatment doesn’t seem to kill the pathogens but makes them impotent,’ he says.

According to Davis, ’a number of pathogens, including viruses, use the same mode of binding: grappling host carbohydrates before infection’. By interfering with the modes of binding, Davis hopes to be able to ’retool the system to almost any target that uses this strategy, simply by changing the sugars and the level of valency of the glycodendrimer’. He thinks that the glycodendriprotein method may be used to construct mimics of almost any naturally occurring glycoproteins. ’There is a wealth of potential applications for such structures in chemical glycobiology and related therapeutic areas. We are pretty excited about what these punters could do,’ exclaims Davis. And it seems that other researchers in the field are keen on the work too, with Anne Dell, professor of carbohydrate chemistry at Imperial College London, considering it to offer ’exciting possibilities’.

Genencor, a US biotechnology company, provided some funding for the work. Davis says that the firm hopes to develop drugs based on the glycodendriproteins. Until now, the project has ’been driven from the academic side’, he says.

Emma Davies