Defining the genetic basis for stress-induced metabolic changes in bacteria

定义细菌应激诱导代谢变化的遗传基础

• 批准号: RGPIN-2020-06015
• 负责人: Navarre, William
• 金额: $ 2.33万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718155
• 关键词: Defining; genetic; basis; stress; induced

Bacteria are living cells that routinely encounter stressful situations and must adapt to survive. Stresses can include acids, detergents, antibiotics, heat, too much salt, toxic metals, and the immune systems of animals that they infect. Bacterial cells can do many things to protect themselves from such stresses including detoxifying or eliminating the cause of stress or by changing some aspect of their physiology (not unlike how a human sweats when they are hot). Not all environments are equal and the way a bacterial cell survives in one environment may be detrimental in another. Bacteria have therefore evolved to link particular stress responses to cues they detect in their local environment. The details of what signals are being sensed and exactly how this information is integrated into an effective response is the focus of this research. In the previous funding cycle the Navarre lab discovered that bacterial sigma factor "S", which is essential for bacterial cells to thrive under several conditions of stress like exposure to antibiotics or detergents and acid stress, dictates whether cells will utilize specific carbon sources. We also observed that sigmaS cells display evidence of metabolic hyperactivity. In exploring the underlying cause of this increased stress susceptibility we noted that normal Salmonella shuts down some of its metabolism (akin to hibernation) when faced with some types of stress while the strains lacking sigmaS do not. A fundamental question is whether these metabolic adjustments render the bacterial cell less susceptible to certain forms stress and what the consequences are if metabolism is not altered. In the upcoming funding period we will determine exactly what parts of metabolism are different in bacterial cells lacking sigmaS under normal growth and under different forms of stress. We will determine if shutting down metabolism renders the bacteria more resistant to specific types of stress and if a failure to shut down metabolism enhances their susceptibility to stress. This work will contribute to a larger body of understanding about how all living forms cope with stress, how metabolism and stress may link to aging and disease, and how metabolism can be manipulated in bacterial cells to make useful chemical products.

细菌是活细胞，它们经常遇到压力，必须适应生存。压力包括酸、洗涤剂、抗生素、热量、过多的盐、有毒金属以及被它们感染的动物的免疫系统。细菌细胞可以做很多事情来保护自己免受这种压力，包括排毒或消除压力的原因，或通过改变生理的某些方面（这与人类在热的时候出汗的方式没什么不同）。并非所有的环境都是平等的，细菌细胞在一种环境中生存的方式可能对另一种环境有害。因此，细菌已经进化到将特定的应激反应与它们在当地环境中检测到的线索联系起来。具体是什么信号被感知，以及这些信息如何被整合到有效的反应中，这些细节是本研究的重点。