Functional and Molecular Analysis of Scout Cell Awakening

侦察细胞觉醒的功能和分子分析

• 批准号: 8444877
• 负责人: Slava Simon Epstein
• 金额: $ 25.35万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8444877
• 关键词: Animals; Antibiotic Therapy; Bacteria; Biological Assay; Biology; Cells; Cessation of life; Characteristics; Chemicals; Cues; Environment; Epigenetic Process; Event; Fractionation; Frequencies; Future; Goals; Growth; Human body; Kinetics; Knowledge; Lead; Life Cycle Stages; Microbe; Microbiologic Phenomena; Modeling; Molecular; Molecular Analysis; Molecular Structure; Mutation; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nature; Noise; Plants; Population; Population Dynamics; Process; Production; Proliferating; Property; Reproduction spores; Rest; Seeds; Signal Transduction; Staging; Starvation; Stochastic Processes; Testing; Time; base; disorder control; environmental change; improved; latent infection; microbial; pathogen; public health relevance; response; tool

DESCRIPTION (provided by applicant): For many bacteria, life cycles between dormancy and activity, and we have recently advanced a new model for the switch between these states. We proposed that dormancy exit is not a response to environmental cues, a characteristic of microbial spores, resting seeds of plants, hibernating animals, among others, but a low frequency, epigenetic, noise-driven, and stochastic process. After awakening, the cells termed "scouts" explore whether or not the environmental conditions are appropriate for growth. The scout strategy guarantees the continued existence of even the smallest population under conditions of environmental challenge, and becomes a particularly important characteristic of pathogenic populations in human body. We present strong evidence that at least some non-spore forming species, such as Mycobacterium smegmatis, and a range of environmental isolates do behave in accordance with the scout model. We show that cells of tested species can remain dormant for weeks and months, wake up from dormancy at dramatically different time points, and after establishing a small proliferating population, produce growth inducing compounds that revive their dormant kin. In this project, we will examine the kinetics of the awakening process and elucidate the chemical nature of the growth inducing factor(s). The gained knowledge will be used in the future to study the biology of slow growing pathogens such as Mycobacterium tuberculosis. This may ultimately lead to better tools for disease control, and is especially relevant to latent infections.

描述（由申请人提供）：对于许多细菌，生命周期在休眠和活动之间，我们最近提出了一种新的模式，用于在这些状态之间切换。我们提出，休眠退出不是对环境线索的响应，不是微生物孢子、植物休眠种子、冬眠动物等的特征，而是一个低频、表观遗传、噪声驱动的随机过程。苏醒后，被称为“侦察兵”的细胞会探索环境条件是否适合生长。侦察兵策略保证了即使是最小的种群在环境挑战条件下的持续存在，成为人体致病性种群的一个特别重要的特征。我们提出了强有力的证据，至少一些非孢子形成的物种，如耻垢分枝杆菌，和一系列环境分离物的行为符合侦察兵模型。我们发现，被测试物种的细胞可以保持休眠数周或数月，在不同的时间点从休眠中醒来，并在建立一个小的增殖群体后，产生诱导生长的化合物，使其休眠的亲属复活。在这个项目中，我们将研究觉醒过程的动力学，并阐明生长诱导因子的化学性质。所获得的知识将在未来用于研究缓慢生长的病原体，如结核分枝杆菌的生物学。这可能最终导致更好的疾病控制工具，特别是与潜伏感染相关。