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

摘要：金黄色葡萄球菌是一种革兰氏阳性细菌病原体，可在医院和社区中引起各种感染。许多抗生素已经成功地用于治疗这种细菌感染，它们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，细菌已经获得了对多种抗菌素的耐药性，在英国，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，确定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，它是合成一种表面结构脂铁酸所必需的。这种蛋白的缺失导致脂壁酸合成停止，并完全阻断葡萄球菌的生长。这些结果表明，LtaS和脂壁酸合成途径可以作为抗生素开发的靶点。这项研究的目的是确定LtaS是否需要在其他人类病原体中生长。此外，本研究还将进一步揭示LtaS酶的作用机制，对今后开发脂磷胆酸合成抑制剂具有重要意义。公众参与：伦敦帝国理工学院有一个专门的新闻办公室，负责通过媒体、研究创始人和感兴趣的慈善机构向公众传播科学。此外，CMMI有一个开放访问的网站，该网站经常更新最新的研究亮点。

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.