Cellular organization, division, and differentiation in an ancient, genetically reduced bacterium

一种古老的基因减少细菌的细胞组织、分裂和分化

• 批准号: 10414941
• 负责人: GEORGE WARREN LIECHTI
• 金额: $ 32.94万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414941
• 关键词: Address; Anabolism; Animal Model; Area; Bacteria; Cell Differentiation process; Cell Shape; Cell Size; Cell Wall; Cell division; Cell physiology; Cells; Cellular Stress; Chlamydia; Chlamydiaceae; Complex; Development; Elements; Environment; Exhibits; Five-Year Plans; Genome; Investigation; Knowledge; Life; Metabolic; Microbe; Modeling; Molecular; Molecular Machines; Organism; Peptidoglycan; Physiological Processes; Process; Role; Series; Stress; System; Work; member; response

Project Summary / Abstract In this proposal we aim to define the molecular mechanisms of division and differentiation in a phylum that consists entirely of bacterial species that live in osmotically stable, intracellular environments. During adaptation to intracellular life, microbes often exhibit a significant reduction in their genome size, resulting in the loss of metabolic and structural elements that are not required for life within a host cell. The bacterial cell wall, composed of peptidoglycan, protects most bacterial species from osmotic stress and is essential for cell division. Peptidoglycan also determines a bacterial cell’s shape, and by directing its synthesis and degradation microbes can effectively control cell size and differentiation between developmental forms. Nascent peptidoglycan biosynthesis is spatially and temporally restricted within bacterial cells via two known molecular complexes: the MreB complex, which is primarily associated with bacterial cell wall synthesis, and the FtsZ complex, which is associated with septal peptidoglycan synthesis required during cell division. Members of the Chlamydiae do not encode FtsZ and have long been thought to completely lack peptidoglycan. We recently discovered that several members of the Chlamydiaceae synthesize peptidoglycan but do not use it to form a canonical cell wall. Instead, these microbes utilize only septal peptidoglycan in their replicative forms, which is maintained, paradoxically, by an MreB complex. Here we propose a series of studies to investigate how members of the Chlamydiaceae temporally and spatially restrict peptidoglycan synthesis throughout the division process, efficiently controlling cell size, division, and the transition between developmental forms. Over the next five years we plan to increase our understanding of these fundamental processes by focusing on three major areas of investigation: 1) Identifying the mechanisms that direct and influence peptidoglycan synthesis and degradation in the absence of FtsZ, 2) characterizing polar localizing features present in Chlamydia and assessing their role in orienting peptidoglycan and the cell division complex, and 3) establishing the critical factors that influence bacterial cell size in an osmotically stable environment during the course of normal development and in response to cell stress. Genetically reduced microbes are attractive models for identifying the fundamental components of essential physiological processes. These planned studies will elucidate not only how genetically reduced microbes regulate cell size and divide in osmotically stable environments, but also illuminate the inherent versatility of the broadly conserved molecular complexes underlying these process.

项目总结/摘要 在这个提议中，我们的目标是定义一个门中分裂和分化的分子机制， 完全由生活在生物学稳定的细胞内环境中的细菌物种组成。期间 为了适应细胞内生活，微生物通常表现出它们的基因组大小的显著减小， 宿主细胞内生命不需要的代谢和结构元素的丧失。细菌细胞 细胞壁由肽聚糖组成，保护大多数细菌免受渗透胁迫，是细胞生长所必需的。 师.肽聚糖还决定了细菌细胞的形状，并通过指导其合成和降解 微生物可以有效地控制细胞大小和发育形式之间的分化。元 肽聚糖生物合成在细菌细胞内通过两种已知的分子生物学途径在空间和时间上受到限制， 复合物：主要与细菌细胞壁合成相关的MreB复合物，以及FtsZ复合物。 复合物，其与细胞分裂期间所需的间隔肽聚糖合成相关。成员 衣原体不编码FtsZ，长期以来被认为完全缺乏肽聚糖。我们最近 发现衣原体科的几个成员合成肽聚糖，但不使用它来形成肽聚糖。 典型细胞壁相反，这些微生物仅利用其复制形式的间隔肽聚糖， 矛盾的是，它是由MreB复合体维持的。在这里，我们提出了一系列的研究，以调查如何 衣原体科的成员在时间和空间上限制肽聚糖的合成， 分裂过程，有效地控制细胞大小，分裂和发育形式之间的过渡。 在未来五年中，我们计划通过关注以下方面来增加对这些基本过程的理解： 研究的三个主要领域：1）确定指导和影响肽聚糖的机制 在不存在FtsZ的情况下的合成和降解，2）表征存在于 衣原体，并评估它们在肽聚糖和细胞分裂复合体的定向中的作用，以及3） 建立在微生物生长过程中在生物稳定环境中影响细菌细胞大小的关键因素， 正常的发育过程和对细胞应激的反应。基因减少的微生物很有吸引力 用于识别基本生理过程的基本组成部分的模型。这些计划 这些研究不仅将阐明基因减少的微生物如何调节细胞大小和在细胞内分裂， 稳定的环境，而且还阐明了广泛保守的分子复合物的固有多功能性 这些过程的基础。