Targeting antibiotic resistance: molecular dissection of a mitotic machine driving genome segregation in Enterococcus

针对抗生素耐药性：驱动肠球菌基因组分离的有丝分裂机器的分子解剖

• 批准号: G0500588/1
• 负责人: Finbarr Hayes
• 金额: $ 37.11万
• 依托单位: University of Manchester
• 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=G0500588%2F1
• 关键词: Targeting; antibiotic; resistance; molecular; dissection

When antibiotics were first identified and developed in the middle of the previous century, it was thought that they would signal an end to many bacterial infectious diseases. To the present day, antibiotics have saved the lives and eased the suffering of countless millions of people. However, in recent decades antibiotic resistant bacteria have emerged inexorably. Of particular concern are those bacteria that acquire resistance to multiple antibiotics as infections caused by these strains can be particularly difficult to treat. The group of bacteria known as enterococci were previously considered to be harmless, perhaps even beneficial, inhabitants of the human gut and many other environments. However, in recent years enterococci have emerged as significant sources of disease among hospital patients who are specially vulnerable to infection. Furthermore, infectious enterococci are often resistant to antibiotics but also are a worrying source of antibiotic resistance spread to other bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Although most of the biochemical processes involved in making bacterial cells, like those of enterococci, are determined by genes located on the bacterial chromosome, many bacteria also harbour accessory elements termed plasmids that can contribute to the genetic make-up of a bacterium. Plasmids are also of considerable medical significance because antibiotic resistance genes are commonly located on these elements which can be transferred rapidly between bacteria thereby leading to the spread of antibiotic resistance. Plasmids have developed genetic strategies that ensure their maintenance within bacteria. This research proposal focuses on an examination of a maintenance system from an antibiotic resistance plasmid in the enterococcus bacterium with a view to enhancing our understanding of how these elements are stably inherited in bacterial populations. By learning more about how plasmids are maintained within bacteria, we hope in the longer term to be able to devise strategies that can be used to destabilize them, thus producing novel antibacterial agents.

当抗生素在上个世纪中叶首次被发现和开发时，人们认为它们将标志着许多细菌传染病的终结。时至今日，抗生素挽救了无数人的生命，减轻了无数人的痛苦。然而，近几十年来，抗药性细菌的出现势不可挡。特别令人担忧的是那些对多种抗生素产生抗药性的细菌，因为这些菌株引起的感染可能特别难以治疗。这种被称为肠球菌的细菌以前被认为是无害的，甚至可能是有益的，居住在人类肠道和许多其他环境中。然而，近年来，肠球菌已经成为医院患者的重要疾病来源，他们特别容易受到感染。此外，感染性肠球菌通常对抗生素具有耐药性，但也是向其他细菌传播抗生素耐药性的令人担忧的来源，如耐甲氧西林金黄色葡萄球菌(MRSA)。尽管像肠球菌一样，制造细菌细胞所涉及的大多数生化过程都是由位于细菌染色体上的基因决定的，但许多细菌也含有被称为质粒的辅助成分，这些成分可以对细菌的遗传构成做出贡献。由于抗生素耐药基因通常位于这些元件上，这些元件可以在细菌之间快速转移，从而导致抗生素耐药性的传播，因此质粒也具有相当的医学意义。质粒已经开发出确保它们在细菌中保持的遗传策略。这项研究的重点是检查肠球菌中抗生素耐药质粒的维持系统，以期加强我们对这些元件如何在细菌群体中稳定遗传的理解。通过更多地了解质粒在细菌中是如何维持的，我们希望从长远来看，能够设计出可以用来破坏它们稳定的策略，从而生产出新的抗菌剂。