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.

鼻疽伯克霍尔德氏菌是类鼻疽的病原体，类鼻疽是一种主要与东南亚和澳大利亚北部有关的疾病。目前尚无针对类鼻疽的既定治疗方法或疫苗。在极端环境条件下生存并引起可能重新激活的潜伏感染使这种病原体很难根除，导致复发感染率很高。由于这些特征，鼻疽杆菌对人类健康和生物防御都具有重要意义。了解体内的生存机制可能有助于了解伯克霍尔德杆菌为何对治疗具有如此抵抗力。已发表的研究表明，4°C 的饥饿条件会导致类鼻疽杆菌细胞的产生，这些细胞无法在标准培养基中生长，并显示出从杆状形态转变为圆形球状形态。这也可以在其他细菌（例如枯草芽孢杆菌）中看到，并推测是所谓的 L 型的形成。这些细胞壁缺陷形式避免了一系列针对细胞壁相关分子的抗生素的杀菌活性。越来越多的证据表明，L 型在人类体内产生，可能是治疗失败和反复感染的原因。最近的一篇论文表明，L 型大肠杆菌是导致复发性尿路感染的原因。该项目旨在制定伯克霍尔德氏菌体外 L 型形成和受感染巨噬细胞中 L 型检测的方案。还将探索用于驱动 L 型和活跃生长状态之间切换的分子机制。该项目的结果将有助于更好地了解这种特殊的细菌形式，这种特殊的细菌形式可能是许多其他治疗失败的原因。