Team CanUK: Novel antibacterial targets, assays, probes and opportunities in bacterial cell wall biogenesis

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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 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. Our progress until recently has been hampered by our inability to routinely synthesise the key chemical components that make this polymer. We can now do this. This is exciting, as we develop the capability to explore important unanswered questions about how bacteria grow and control the production of peptidoglycan. We wish to pull together the expertise of UK and Canadian scientists in a cooperative and coordinated partnership to increase our understanding of the fundamental biology of this process. All of this will open fundamentally new biological insights, and opportunities to use these for the future development of new antibiotics that will work against multiply antibiotic resistant bacteria like MRSA and TB.