Novel Chemical Probes of Surface-Layer Formation in Pathogenic Bacteria

这项拟议中的研究旨在开发新的化学技术，使我们能够了解C。艰难梭菌产生其高度抗性的结晶外壳，这是其在用广谱抗生素治疗后在人体内持续存在的关键机制。面对日益广泛的抗生素耐药性感染，迫切需要提高我们对病原菌基本生物学的理解，然后在此基础上找到抑制细菌生长的新机制。C.艰难梭菌是最致命的医院感染之一，仅在英国2005年就记录了超过3800例死亡（参见2000年由于MRSA），相应的资源消耗是NHS的重大负担。通过这项工作产生的信息可能会提供一个新的路线目标C。艰难梭菌，可以规避其通常的抗生素耐药性。同样重要的是化学技术的进步，这可能使我们能够对相关物种（如C。破伤风，引起破伤风的细菌）和相关的致病过程（例如细菌毒素的释放和加工）。

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).