Conservation and biochemical characterization of the essential Staphylococcus aureus lipoteichoic acid synthase LtaS

金黄色葡萄球菌脂磷壁酸合酶 LtaS 的保护和生化特性

• 批准号: G0701212/1
• 负责人: Angelika Grundling
• 金额: $ 47.12万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701212%2F1
• 关键词: Conservation; biochemical; characterization; essential; Staphylococcus

Lay Summary:Staphylococcus aureus is a Gram-positive bacterial pathogen that can cause a variety of infections both in hospital settings as well as in the community. Many antibiotics, which have been successfully used to treat such bacterial infections, kill the bacterium by inhibiting the production of important surface-structures. However, an alarming aspect of staphylococcal infections is that bacteria have acquired resistance to multiple antimicrobials and the infection rate with methicillin-resistant S. aureus strains (MRSA) within the UK is amongst the highest in developed countries. Therefore, it is important to identify and validate alternative ways to inhibit staphylococcal growth. I have recently identified a protein named LtaS, which is required for the synthesis of a surface structure called lipoteichioc acid. Depletion of this protein caused a halt in lipoteichioc acid synthesis and completely blocked staphylococcal growth. These results suggest that LtaS and the lipoteichioc acid synthesis pathway can serve as targets for antibiotic development. This study aims to determine if LtaS is required for growth in other human pathogens. In addition, the proposed work will give insight into the mechanism of action of the enzyme LtaS, which will be of great benefit for the future development of lipoteichioc acid synthesis inhibitors. Public engagement:Imperial College London has a dedicated press office that is responsible for the public dissemination of science through the media and with research founders and interested charities. Furthermore, the CMMI has an open-access website which is frequently updated with recent research highlights.

摘要：金黄色葡萄球菌是一种革兰氏阳性细菌病原体，可在医院环境和社区引起多种感染。许多已成功用于治疗此类细菌感染的抗生素通过抑制重要表面结构的产生来杀死细菌。然而，葡萄球菌感染的一个令人担忧的方面是，细菌已经对多种抗菌药物产生了耐药性，并且英国耐甲氧西林金黄色葡萄球菌菌株（MRSA）的感染率是发达国家中最高的。因此，识别和验证抑制葡萄球菌生长的替代方法非常重要。我最近发现了一种名为 LtaS 的蛋白质，它是合成脂磷壁酸表面结构所必需的。这种蛋白质的消耗导致脂磷氯酸合成停止并完全阻止葡萄球菌生长。这些结果表明 LtaS 和脂磷壁酸合成途径可以作为抗生素开发的靶点。本研究旨在确定其他人类病原体的生长是否需要 LtaS。此外，该工作将深入了解LtaS酶的作用机制，这对于脂磷壁酸合成抑制剂的未来发展将大有裨益。公众参与：伦敦帝国理工学院设有专门的新闻办公室，负责通过媒体以及研究创始人和感兴趣的慈善机构向公众传播科学。此外，CMMI 有一个开放访问网站，经常更新最新的研究亮点。