UK-BaCWAN: UK-Bacterial Cell Wall Assembly Network

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Millions of people die each year from bacterial infections and tens of millions suffer from the consequences of these infections. The discovery of the antibiotic penicillin once opened the door to treat these infections by stopping bacteria making the polymer in the cell wall that holds them together. This polymer, called peptidoglycan, is made up of an interlocking network of sugars and strings of amino acids (peptides). Specialised proteins (called PBPs), with the ability to stitch together these sugars and peptides are the targets inhibited by penicillin, stopping cell wall synthesis and killing the bacterium. Many important bacteria are now no longer killed by penicillin and other antibiotics that attack other stages in the production of peptidoglycan. Bacteria have changed, evading the action of these antibiotics. We need to fight back, by using the advanced computing power at our disposal to design new classes of antibiotics, compounds that will work against multiply resistant bacteria like MRSA, and help combat the harmful effects of our immune system when it over responds to infection. The group at Warwick has brought together a UK-wide team from microbiology, biochemistry, chemistry, structural biology, physiology, engineering and mathematics to crack this problem. They will have, for the first time, the combined tools and new chemical reagents (to be made for the team at a cost efficient central location at Warwick) to look in minute detail how peptidoglycan is made, how we could stop this process by the development of new inhibitors (antibiotics) and how fragments of peptidoglycan interact with our bodies during the process of infection. This capacity for discovery, being lost elsewhere, will provide a unique forum for the development of new compounds.