UK-BaCWAN: UK-Bacterial Cell Wall Assembly Network

UK-BaCWAN：英国细菌细胞壁组装网络

• 批准号: G0500643/1
• 负责人: David Ian Roper
• 金额: $ 21.02万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0500643%2F1
• 关键词: UK; BaCWAN; Bacterial; Cell; Wall

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.

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。抗生素青霉素的发现曾经打开了治疗这些感染的大门，通过阻止细菌在细胞壁中制造聚合物来将它们结合在一起。这种聚合物称为肽聚糖，由糖和氨基酸（肽）链的联锁网络组成。具有将这些糖和肽缝合在一起的能力的专门蛋白质（称为PBPs）是青霉素抑制的目标，停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，这些抗生素攻击肽聚糖生产的其他阶段。细菌发生了变化，逃避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，这些化合物将对MRSA等多重耐药细菌起作用，并帮助对抗我们的免疫系统对感染过度反应时的有害影响。沃里克的研究小组汇集了来自微生物学、生物化学、化学、结构生物学、生理学、工程学和数学的全英国团队来解决这个问题。他们将首次拥有组合工具和新的化学试剂（将在沃里克的一个具有成本效益的中心位置为团队制造），以详细了解肽聚糖是如何制造的，我们如何通过开发新的抑制剂（抗生素）来阻止这一过程，以及肽聚糖片段如何在感染过程中与我们的身体相互作用。这种发现的能力，在其他地方正在失去，将为新化合物的开发提供一个独特的论坛。