Novel Chemical Probes of Surface-Layer Formation in Pathogenic Bacteria

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The proposed research aims to develop novel chemical technologies that will enable us to understand how C. difficile generates its highly-resistant crystalline outer coating, a key mechanism by which it persists in the human body after treatment with broad-spectrum antibiotics. In the face of increasingly wide-spread antibiotic resistant infection, there is a pressing need to improve our understanding of the basic biology of pathogenic bacteria and then build on this work to find novel mechanisms to inhibit bacterial growth. C. difficile is one of the most lethal hospital infections, with over 3800 deaths recorded in 2005 in the UK alone (c.f. 2000 due to MRSA), and the corresponding drain on resources is a significant burden on the NHS. The information generated by this work may provide a new route to target C. difficile that can circumvent its usual antibiotic resistance. Of equal significance are the proposed advances in chemical technology, which may enable comparable insights into related species (e.g. C. tetani, the bacterium that causes tetanus) and related pathogenic processes (e.g. release and processing of bacterial toxins).