Does stripping the cell wall promote survival of Burkholderia in an infected host?

剥离细胞壁是否会促进伯克霍尔德杆菌在受感染宿主体内的存活？

• 批准号: 2593085
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2593085
• 关键词: Does; stripping; cell; wall; promote

Burkholderia pseudomallei is the causative agent of Melioidosis, a disease predominantly linked to South East Asia and Northern Australia. Currently there are no established treatments or vaccines for Melioidosis. Surviving extreme environmental conditions and causing latent infections which can become reactivated make this pathogen very hard to eradicate, leading to high rates of recurrent infection. B. pseudomallei is of importance for both human health and biodefense due to these features. Understanding the survival mechanisms in vivo will potentially give insights into why Burkholderia are so resistant to treatments. Published research indicates that starvation conditions at 4C leads to the generation of B. pseudomallei cells which cannot grow in standard media and show a conversion from rods to a rounded coccoid morphology. This can also be seen in other bacteria such as Bacillus subtilis and hypothesized to be the formation of so-called L-forms. These cell wall deficient forms avoid the bactericidal activity from an array of antibiotics which target cell wall related molecules. Increasing evidence suggests L-forms are generated in humans and could be reason for failed treatment and recurrent infections. A recent paper shows Eschericia coli L-forms were responsible for recurrent urinary tract infections. This project will be aimed to produce a protocol for in vitro L-form formation of Burkholderia species and the detection of L-forms in infected macrophages. The molecular mechanisms which are employed to drive the switching between L-form and actively growing states will also be explored. The results of this project will give a better insight into this special bacterial form which has potential to be the cause of many other treatment failures.

Burkholderia pseudomallei是Melioidosis的病因，这是一种与东南亚和澳大利亚北部有关的疾病。目前尚无固定治疗方法或疫苗的黑梅利病症。幸存的极端环境条件并引起潜在感染，可以重新激活这种病原体很难根除，从而导致高复发感染率。 B.假乳核对这些特征对于人类健康和生物陷入困境至关重要。了解体内的生存机制将有可能深入了解为什么Burkholderia对治疗具有抗药性。已发表的研究表明，4C处的饥饿条件会导致假芽孢杆菌细胞的产生，这些细胞无法在标准培养基中生长，并显示从杆上转化为圆形的球形形态。这也可以在其他细菌（例如枯草芽孢杆菌）中看到，并假设是所谓的L形成。这些细胞壁缺乏形式避免了靶向细胞壁相关分子的一系列抗生素的杀菌活性。越来越多的证据表明，人类产生了L形式，可能是治疗失败和复发感染的原因。最近的一篇论文表明，大肠杆菌L形式是导致复发性尿路感染的原因。该项目将旨在生成用于体外L形成Burkholderia物种的方案，并在感染的巨噬细胞中检测L形式。还将探索用于驱动L形和积极生长状态之间切换的分子机制。该项目的结果将使您可以更好地了解这种特殊的细菌形式，这有可能成为许多其他治疗失败的原因。