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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761248
• 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.

细菌是常规遇到压力情况并必须适应生存的活细胞。应力可以包括酸，洗涤剂，抗生素，热量，过多的盐，有毒金属以及它们感染的动物的免疫系统。细菌细胞可以做许多事情来保护自己免受这种压力，包括排毒或消除压力原因或通过改变其生理学的某些方面（与人类热时汗水的汗水不同）。并非所有环境都是相等的，并且细菌细胞在一个环境中生存的方式可能在另一种环境中有害。因此，细菌已经演变为将特定的压力反应与他们在本地环境中检测到的线索联系起来。这项研究的重点是感知哪些信号的详细信息以及如何将此信息集成到有效的响应中。 在先前的资金周期中，纳瓦尔实验室发现细菌sigma因子“ s”，这对于细菌细胞在多种压力条件下繁衍至关重要，例如暴露于抗生素或洗涤剂和酸应激，决定了细胞是否利用特定的碳源。我们还观察到Sigmas细胞显示了代谢多动症的证据。在探索这种应力易感性增加的根本原因时，我们注意到正常的沙门氏菌会在面临某些类型的压力而缺乏西格马斯的菌株的情况下关闭其某些新陈代谢（类似于冬眠）。 一个基本的问题是，这些代谢调整是否会使细菌细胞不太容易受到某些形式的压力，以及如果不改变代谢会带来什么后果。在即将到来的资金期间，我们将准确确定在正常生长和不同形式的压力下缺乏闪光的细菌细胞中哪些代谢的部分不同。我们将确定关闭新陈代谢是否会使细菌对特定类型的压力具有更大的抵抗力，以及未能关闭代谢会增强其对压力的敏感性。这项工作将有助于对所有生活形式如何应对压力，新陈代谢和压力如何与衰老和疾病联系在一起以及如何在细菌细胞中操纵新陈代谢以制造有用的化学产品。