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

细菌是活细胞，经常遇到压力环境，必须适应才能生存。压力可能包括酸、洗涤剂、抗生素、高温、过多的盐、有毒金属以及它们感染的动物的免疫系统。细菌细胞可以做很多事情来保护自己免受这种压力，包括解毒或消除压力的原因，或者通过改变它们生理的某些方面(就像人类在热的时候出汗一样)。并不是所有的环境都是平等的，细菌细胞在一个环境中的生存方式在另一个环境中可能是有害的。因此，细菌进化成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。什么信号被感知到，以及这些信息究竟如何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Sigma因子“S”决定了细胞是否会利用特定的碳源。“Sigma因子”是细菌细胞在抗生素或洗涤剂以及酸胁迫等压力条件下茁壮成长所必需的。我们还观察到Sigma细胞表现出代谢亢进的证据。在探索这种压力敏感性增加的根本原因时，我们注意到，正常的沙门氏菌在面临某些类型的压力时会关闭其某些新陈代谢(类似于冬眠)，而缺乏Sigma的菌株则不会。一个根本的问题是，这些新陈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的影响，如果新陈代谢没有改变，会有什么后果。在即将到来的资助期间，我们将准确地确定缺乏Sigma的细菌细胞在正常生长和不同形式的压力下代谢的哪些部分是不同的。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更具抵抗力，以及未能关闭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，新陈代谢和压力可能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来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 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.