UK-BaCWAN: UK-Bacterial Cell Wall Assembly Network

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.

Bacterial cell wall assembly is an important target for the development of novel antibacterial agents, and is intimately connected with the emergence of antibiotic resistance around the world. There are significant research programmes carried out in UK laboratories in this area, but at present these activities are somewhat fragmented, with groups in Chemistry, Biochemistry, and Microbiology departments following different areas related to this problem. Therefore we propose to establish a UK Network in bacterial cell wall assembly, which can bring together expertise different disciplines and provide a forum for the additional involvement of industrial and physical scientists, to inform the network of industrial interests and emerging physical techniques. The principal vehicle for this network will be a series of bi-yearly meetings involving chemists, biochemists, microbiologists, computational, industrial and physical scientists to stimulate new inter-disciplinary research and collaboration in this area. The establishment of a web site to distribute information to members, other scientists and the general public will also augment these meetings. We also wish to facilitate new collaborative research programmes that will arise from this network by funding inter-laboratory and interdisciplinary visits for students, postdoctoral researchers and PIs, enabling technology and technique transfer to stimulate future research efforts within the UK scientific community.