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

当抗生素在上个世纪中期首次被发现和开发时，人们认为它们将标志着许多细菌性传染病的终结。时至今日，抗生素已经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，抗生素耐药性细菌已经不可阻挡地出现。特别值得关注的是那些对多种抗生素产生耐药性的细菌，因为由这些菌株引起的感染特别难以治疗。被称为肠球菌的细菌群以前被认为是无害的，甚至可能是有益的，人类肠道和许多其他环境的居民。然而，近年来，肠球菌已成为医院患者中特别容易感染的重要疾病来源。此外，传染性肠球菌通常对抗生素具有耐药性，但也是令人担忧的抗生素耐药性传播到其他细菌如耐甲氧西林金黄色葡萄球菌（MRSA）的来源。虽然大多数涉及制造细菌细胞的生化过程，如肠球菌，是由位于细菌染色体上的基因决定的，但许多细菌也含有称为质粒的辅助元件，这些元件可以有助于细菌的遗传组成。质粒也具有相当大的医学意义，因为抗生素抗性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，从而导致抗生素抗性的传播。原生质体已经开发出确保其在细菌内维持的遗传策略。这项研究计划的重点是检查肠球菌细菌中抗生素耐药性质粒的维持系统，以提高我们对这些元件如何在细菌种群中稳定遗传的理解。通过更多地了解质粒是如何在细菌内维持的，我们希望从长远来看能够设计出可用于破坏它们的稳定性的策略，从而产生新型抗菌剂。

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.