Exploring the Role of Bacterial Translation Factors in Metabolism and Stress Resistance

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。***在上一个资助周期中，纳瓦拉实验室发现细菌含有一种叫做“延伸因子P”或EF-P的蛋白质，这种蛋白质对细菌细胞在几种压力条件下（如暴露于抗生素或洗涤剂和酸性压力下）茁壮成长至关重要。在这项工作的过程中，我们还观察到EF-P细胞表现出代谢亢进的迹象。在探索这种压力敏感性增加的潜在原因时，我们注意到，当面临某些类型的压力时，正常沙门氏菌会关闭其某些代谢（类似于冬眠），而缺乏EF-P的菌株则不会。一个基本的问题是，降低代谢是否会使细菌细胞对某些形式的压力不那么敏感，如果不降低代谢会产生什么后果。在即将到来的资助期内，我们将确切地确定在正常生长和不同形式的压力下，缺乏EF-P的细菌细胞的代谢部分是不同的。我们将确定停止新陈代谢是否会使细菌对特定类型的压力更具抵抗力，以及停止新陈代谢是否会增加它们对压力的敏感性。这项工作将有助于更广泛地了解所有生命形式如何应对压力，新陈代谢和压力如何与衰老和疾病联系起来，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。***********

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 bacteria contain a protein called "elongation factor P" or EF-P that is essential for bacterial cells to thrive under several conditions of stress like exposure to antibiotics or detergents and acid stress. During the course of this work we also observed that EF-P 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 EF-P do not. ***A fundamental question is whether lowering metabolism renders the bacterial cell less susceptible to certain forms stress and what the consequences are if metabolism is not lowered. In the upcoming funding period we will determine exactly what parts of metabolism are different in bacterial cells lacking EF-P 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.***********