Mechanisms and implications of two-component signal transduction in Campylobacter jejuni

细菌对不同条件的感知和反应能力对它们的生存至关重要。实施这一点的一个保守方法是双组分信号转导系统(TCS)。在典型的双组分系统中，细菌表面的传感器蛋白感知外部信号，并激活细胞质中的调节蛋白。然后，该调节器结合DNA来改变基因表达，进而改变细菌对信号的反应行为。 我们研究的生物，空肠弯曲杆菌，是一种普遍存在的肠道病原体，最适合在鸡等共生动物宿主体内生活。然而，它也可以在不利的环境中生存(并经常茁壮成长)，如水和食品加工厂、泥土、杂货店的家禽表面以及易受感染的人类宿主。矛盾的是，空肠弯曲菌基因组中TCSs等调控基因的比例比其他肠道细菌(如大肠杆菌)要小得多，更类似于人类胃部受限的幽门螺杆菌。 这些观察结果使我们假设，空肠弯曲菌中的关键TC将控制空肠弯曲菌生活的多个方面。事实上，我们已经发现，构成该研究计划基础的TCS是鸡生存所必需的，也是调节细菌生理学的关键方面。这项研究计划的目标是确定这些系统直接和间接影响哪些基因，探索可能与这些系统相互作用的其他细菌因素，并揭示系统对哪些信号做出反应。这将为控制空肠弯曲菌行为的重要机制提供洞察，并为其他可能同样需要使用有限的监管机制穿越不同生态位的生物提供模型。

The ability of bacteria to sense and respond to different conditions is essential to their survival. A conserved means to enact this is the two-component signal transduction system (TCS). In typical two-component systems, a sensor protein on the bacterial surface senses an external signal and activates a regulator protein in the cytoplasm. The regulator then binds DNA to alter gene expression, which in turn alters bacterial behavior in response to the signal. The organism we study, Campylobacter jejuni, is a prevalent enteric pathogen that lives optimally inside commensal animal hosts such as chickens. However, it can also survive (and often thrive) in unfavorable environments such as water and food processing plants, in the dirt, and on poultry surfaces in the grocery store, as well as within susceptible human hosts. Paradoxically, the percentage of the C. jejuni genome devoted to regulatory genes such as TCSs is much smaller than that of other enteric bacteria like E. coli and more similar to the human stomach-restricted Helicobacter pylori. These observations led us to hypothesize that critical TCSs in C. jejuni will control multiple aspects of the C. jejuni lifestyle. Indeed, we have found that the TCSs that form the basis of this research program are required for survival in chickens and also modulate key aspects of bacterial physiology. The goal of this research program is to identify which genes these systems influence both directly and indirectly, explore other bacterial factors that may interact with these systems, and reveal signals to which the systems respond. This will provide insight into important mechanisms governing C. jejuni behavior and provide models for other organisms which may likewise need to traverse diverse niches using limited regulatory machinery.