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.

细菌是活细胞，经常遇到压力的情况下，必须适应生存。压力可以包括酸，洗涤剂，抗生素，热，太多的盐，有毒金属，以及它们感染的动物的免疫系统。细菌细胞可以做很多事情来保护自己免受这种压力的影响，包括解毒或消除压力的原因，或者改变它们生理学的某些方面（这与人类在炎热时出汗的方式不同）。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在另一种环境中是有害的。因此，细菌已经进化到将特定的压力反应与它们在当地环境中检测到的线索联系起来。什么样的信号被感知的细节，以及这些信息是如何被整合到一个有效的反应是这项研究的重点。 在上一个资助周期中，纳瓦拉实验室发现，细菌西格玛因子“S”决定了细胞是否会利用特定的碳源，该因子是细菌细胞在暴露于抗生素或洗涤剂和酸应激等多种应激条件下茁壮成长所必需的。我们还观察到sigmaS细胞显示代谢亢进的证据。在探索这种应激易感性增加的根本原因时，我们注意到，当面临某些类型的应激时，正常的沙门氏菌会关闭其部分代谢（类似于冬眠），而缺乏sigmaS的菌株则不会。 一个基本的问题是，这些代谢调节是否使细菌细胞对某些形式的压力不那么敏感，如果代谢不改变，后果是什么。在即将到来的资助期间，我们将确定在正常生长和不同形式的压力下，缺乏sigmaS的细菌细胞中代谢的哪些部分是不同的。我们将确定关闭代谢是否会使细菌对特定类型的压力更具抵抗力，以及未能关闭代谢是否会增强它们对压力的易感性。这项工作将有助于更广泛地了解所有生命形式如何科普压力，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。