Nucleic Acid Synthesis and Cell Division in Model Pathogenic Bacteria

近年来，抗生素耐药性的上升，特别是在医院，除了感染者的个人成本外，还给卫生系统带来了巨大的经济负担。在过去的60年里，我们已经习惯了可以有效治疗大多数(如果不是全部)细菌感染的抗生素的供应。如今，情况并非如此，医院里的一些细菌对所有治疗有用的抗生素都具有抗药性。药物开发的成本非常可观；从制药公司的财务角度来看，新抗生素的从头开发并不具有吸引力，因为它们只是短期使用的药物。收回开发成本需要很长时间。因此，目前正在开发的新抗生素很少，许多较新的抗生素是学术努力和随后成立的衍生公司的结果，这些公司开发新药一直到第一阶段试验。迫切需要新的、有效的抗生素疗法。我们建议确定和验证关键基本生物学过程的使用，作为开发两种重要医院病原体的新抗菌剂的目标。金黄色葡萄球菌是一种广为人知的病原体，是医院获得性(医院内)感染的头号原因。不动杆菌属。在医院感染中是一个相对较新的问题，但由于它能够以惊人的速度对抗生素产生抗药性，其重要性正在增长。在这两种生物中，我们打算以参与DNA复制(遗传物质的复制)、转录(产生遗传信息)和细胞分裂的基本蛋白质-蛋白质相互作用为目标。以蛋白质相互作用为靶点，而不是以蛋白质的酶活性为靶点，为抗菌开发提供了一条新的、尚未开发的途径，具有巨大的成功潜力。

The rise of antibiotic resistance, particularly in hospitals, over recent years represents a huge financial burden on the health system, in addition to the personal costs to the patient infected. Over the last 60 years, we have become accustomed to the availability of antibiotics that can effectively treat most, if not all, bacterial infections. Today, this is not the case, and some bacteria in hospitals are resistant to all therapeutically useful antibiotics. The costs of drug development are very considerable; from the financial perspective of a pharmaceutical company, the de novo development of new antibiotics is not attractive because they are drugs that are only used for a short period. Recoupment of development costs takes a long time. As a result, very few new antibiotics are currently in development, and many of the newer ones are the result of academic efforts and subsequent formation of spin-out companies that develop new drugs through to phase 1 trials. The need for new, and effective, antibiotic therapies is pressing. We propose to identify and validate the use of key essential biological processes as targets for the development of new antimicrobial agents in two important hospital pathogens. Staphylococcus aureus is a well known and established pathogen that is the number one cause of hospital acquired (nosocomial) infections. Acinetobacter sp. is a relatively new problem in nosocomial infections, but is growing in importance due to the startling rate at which it is able to acquire resistance to antibiotics. In both organisms, we intend to target essential protein-protein interactions involved in DNA replication (duplication of genetic material), transcription (production of a genetic message), and cell division. The targeting of protein-protein interactions, rather than the enzymic activity of a protein provides a novel and unexploited avenue for antibacterial development with great potential for success.