UK-BaCWAN: UK-Bacterial Cell Wall Assembly Network

每年有数百万人死于细菌感染，数千万人遭受这些感染的后果。抗生素盘尼西林的发现曾经为通过阻止细菌在细胞壁中制造将它们结合在一起的聚合物来治疗这些感染打开了大门。这种聚合物被称为肽聚糖，是由糖和氨基酸链（肽）组成的连锁网络。有能力将这些糖和肽结合在一起的特殊蛋白质（称为PBPs）是青霉素抑制的目标，阻止细胞壁合成并杀死细菌。许多重要的细菌现在不再被青霉素和其他抗生素杀死，这些抗生素会攻击肽聚糖生产的其他阶段。细菌已经发生了变化，避开了这些抗生素的作用。我们需要反击，利用我们掌握的先进计算能力来设计新型抗生素和化合物，这些化合物可以对抗像MRSA这样的多重耐药细菌，并帮助对抗免疫系统对感染的过度反应带来的有害影响。华威大学的研究小组召集了一个来自英国范围内的团队，包括微生物学、生物化学、化学、结构生物学、生理学、工程学和数学，来解决这个问题。他们将首次使用组合工具和新的化学试剂（将在华威大学的一个经济高效的中心位置为团队制造）来详细研究肽聚糖是如何产生的，我们如何通过开发新的抑制剂（抗生素）来阻止这一过程，以及肽聚糖片段在感染过程中如何与我们的身体相互作用。这种在其他地方失去的发现能力，将为开发新化合物提供一个独特的论坛。

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.