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.

项目概要/摘要 在这个提案中，我们的目标是定义一个门中分裂和分化的分子机制， 完全由生活在渗透稳定的细胞内环境中的细菌物种组成。 为了适应细胞内的生活，微生物的基因组大小通常会显着减小，从而导致 宿主细胞内生命不需要的代谢和结构元素的损失。 由肽聚糖组成的壁可保护大多数细菌物种免受渗透压的影响，并且对于细胞的生存至关重要 肽聚糖还决定细菌细胞的形状，并指导其合成和降解。 微生物可以有效地控制细胞大小和发育形式之间的分化。 肽聚糖生物合成通过两种已知的分子在空间和时间上限制在细菌细胞内 复合物：MreB 复合物，主要与细菌细胞壁合成相关，以及 FtsZ 复合物，与细胞分裂过程中所需的间隔肽聚糖合成有关。 衣原体不编码 FtsZ，并且长期以来一直被认为完全缺乏肽聚糖。 发现衣原体科的一些成员合成肽聚糖，但不使用它形成肽聚糖 相反，这些微生物仅利用其复制形式的隔膜肽聚糖。 矛盾的是，它是由 MreB 复合体维持的。在这里，我们提出了一系列研究来调查它是如何维持的。 衣原体科成员在时间和空间上限制肽聚糖的合成 分裂过程，有效控制细胞大小、分裂和发育形式之间的过渡。 在接下来的五年中，我们计划通过重点关注来加深对这些基本过程的理解 三个主要研究领域：1）确定指导和影响肽聚糖的机制 在没有 FtsZ 的情况下的合成和降解，2) 表征存在于中的极性定位特征 衣原体并评估其在定向肽聚糖和细胞分裂复合物中的作用，以及 3) 确定在渗透稳定环境中影响细菌细胞大小的关键因素 正常发育过程和对细胞应激的反应具有吸引力。 用于识别基本生理过程的基本组成部分的模型。 研究不仅将阐明基因减少的微生物如何调节细胞大小和渗透分裂 稳定的环境，同时也阐明了广泛保守的分子复合物固有的多功能性 这些过程的基础。