How does tuberculosis eat its own cell wall?

结核病如何吃掉自己的细胞壁？

• 批准号: 2266957
• 金额: --
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2266957
• 关键词: How; does; tuberculosis; eat; its

Mycobacteria possess one of the most intricately designed and complex cell walls within the bacterial kingdom. The components that make up the cell wall all significantly contribute to the virulence of mycobacteria both agriculturally and in humans i.e. in important animals such as cows (e.g. Mycobacterium bovis) and humans (Mycobacterium tuberculosis) respectively. The base-layer of the mycobacterial cell wall is comprised of a heteropolymer called peptidoglycan. This glycan-peptide conjugate protects the cell from its turgor pressure, and provides a scaffold for the entire cell wall. Despite its importance we have an incomplete knowledge of how this wall is constructed and dissembled. In other organisms PBPs have been identified to a plethora of roles in peptidoglycan synthesis/remodelling. The M. tuberculosis genome encodes more than ten penicillin binding proteins, most of which the functions have not been explored. Key functional involvement for PBPs such as cell division and elongation have been shown to be important for organisms such as E. coli. This study will investigate and identify the function of the mycobacterial PBPs in M. tuberculosis. To understand the biosynthesis, remodeling and degradation of M. tuberculosis peptidoglycan, we will take advantage of an ordered, single-gene deletion library in M. bovis BCG as well as targeted mutational studies in strains of Mycobacterium marinum, Mycobacterium smegmatis, M. tuberculosis and E. coli. We will evaluate the fitness of strains lacking each of the non-essential PBPs under a wide variety of conditions, so that we can better understand the role of individual PBPs to the organism. This will allow us to determine if individual PBPs become more important under stress such as pH variation, redox or antimicrobial compounds which are all relevant to M. tuberculosis infection. Morphological studies will determine if the loss of any PBPs result in defects in cell division or shape. This will be paired with biochemical and structural analysis of purified PBPs to allow us to interrogate their catalytic function. This project will give us a better understanding of the mechanisms M. tuberculosis utilises for reproduction and survival in the context of environmental and infection dynamics.

分枝杆菌拥有细菌王国中最复杂的细胞壁之一。构成细胞壁的组分都显著地有助于农业上和人类中分枝杆菌的毒力，即分别在重要动物如牛（例如牛分枝杆菌）和人类（结核分枝杆菌）中。分枝杆菌细胞壁的基层由称为肽聚糖的杂聚物组成。这种聚糖-肽缀合物保护细胞免受膨压，并为整个细胞壁提供支架。尽管它的重要性，我们有一个不完整的知识，这堵墙是如何建造和拆除。在其他生物体中，已确定PBP在肽聚糖合成/重塑中具有过多的作用。分枝结核杆菌基因组编码十余种青霉素结合蛋白，其中大部分功能尚不清楚。PBPs的关键功能参与，如细胞分裂和延伸，已被证明是重要的生物体，如大肠杆菌。杆菌本研究将探讨和鉴定分枝杆菌PBP在M.结核了解M.结核分枝杆菌肽聚糖，我们将利用一个有序的，单基因缺失文库在M。牛BCG以及在海洋分枝杆菌、耻垢分枝杆菌、M.结核和E.杆菌我们将在各种条件下评估缺乏每种非必需PBPs的菌株的适应性，以便我们能够更好地了解单个PBPs对生物体的作用。这将使我们能够确定单个PBP是否在压力下变得更重要，例如pH变化，氧化还原或抗菌化合物，这些都与M相关。肺结核感染。形态学研究将确定任何PBPs的丢失是否会导致细胞分裂或形状的缺陷。这将与纯化的PBPs的生物化学和结构分析配对，使我们能够询问它们的催化功能。该项目将使我们更好地了解机制M。结核病在环境和感染动力学的背景下用于繁殖和生存。