Chemosensory transduction and the cytoplasmic pathway of Rhodobacter sphaeroides

大多数细菌都会游泳，并利用这种游泳来达到它们生长的最佳环境。这可能是植物的根，可能是伤口，也可能是感染的肠壁，也可能是，例如，生长的最佳氧气浓度。细菌太小了，无法感知空间梯度，但已经开发出一种极其敏感的时间传感系统，可以在大范围的背景浓度范围内感知到小到几个分子的变化。它们感觉到这些变化，并向旋转鞭毛马达发出信号，使它们的游泳偏向更好的环境。这种敏感性的起源几十年来一直困扰着研究人员。利用“主力”细菌E.Coli，研究表明，参与感受和传递趋化信号的蛋白质在细胞两极形成了一个非常大的感觉复合体，即一系列相互作用的蛋白质。蛋白质相互作用的动态似乎允许受体适应当前的变化，让邻近的受体能够对未来的变化做出反应。这种允许提高灵敏度的蛋白质相互作用模型对其他感觉系统的整个范围都有影响。因此，这个模型不仅适用于大肠杆菌，还适用于其他物种，这一点很重要。许多其他细菌有不止一条途径。这似乎可能允许这些物种调整它们对当前生长条件的反应，不同的途径在不同的生长条件下是重要的，甚至可能阻止来自一条途径的信号，如果新陈代谢不能从该养分的增加中受益的话。我们有兴趣了解情况是否如此，以及了解来自不同途径的信号如何整合以产生平衡的反应。我们以前的研究表明，不同通路的蛋白质是有针对性的，因此它们形成离散的感觉复合体，防止不同通路过早地相互作用。在细胞分裂时，用于维持子代细胞中正确数量的途径复合体的机制似乎与确保细胞在中间分裂以及每个子代在分裂时具有正确的细胞质互补的机制有关。这些数据表明，细菌的发育机制比之前认为的要复杂得多。因此，这项研究的一部分将集中在确定化学感觉途径的组织形成所涉及的机制，确保每个子细胞获得具有正确蛋白质补充的感觉复合体，以便每个子细胞在分裂时能够做出化学感觉反应。人们认为，大肠杆菌感觉通路对几个分子的敏感性取决于受体的重新设置，从而允许其他受体现在做出反应。其他物种的受体往往不同于大肠杆菌的受体，而且适应区域很难识别。如果同样的系统适用，我们需要识别其他受体上的相关位置，这将成为该项目的一部分，测试是否可以为所有细菌的游泳行为开发一个通用模型。这些数据将显示大肠杆菌化学感觉模型的哪些方面可以扩展到其他细菌物种，在这种情况下，是球形红杆菌，以及确保子细胞包含相同DNA和蛋白质的组织机制是否相关，从而允许开发细菌生长的复杂发育模型。

Most bacteria swim, and use that swimming to reach their optimum environment for growth. This could be a plant root, it could be a wound or the gut wall for infection or it could be, for example, the optimum oxygen concentration for growth. Bacteria are too small to sense a spatial gradient, but have developed an exquisitely sensitive temporal sensing system that can sense a change as small as a few molecules over a wide range of background concentrations. They sense these changes and signal to a rotary flagellar motor to bias their swimming towards a better environment. The origins of this sensitivity have puzzled researchers for decades. Using the 'workhorse' bacterium, E.coli, it has been shown that the proteins involved in sensing and transducing the chemotaxis signal form a very large sensory complex, a raft of interacting proteins, at the cell poles. The dynamics of the interactions of the proteins appears to allow the receptors to adapt to current changes, leaving the neighbouring receptors able to respond to future changes. This model of interaction of proteins allowing increased sensitivity has implications for a whole range of other sensory systems. It therefore matters that this model applies to species other than just E.coli. Many other bacteria have more than one pathway. It seems probable that this allows these species to tune their responses to current growth conditions, with the different pathways being important under different growth conditions and perhaps even blocking signals from one pathway if metabolism will not benefit from an increase in availability of that nutrient. We are interested to see whether this is the case, and to understand how the signals from the different pathways integrate to produce a balanced response. Our previous studies showed that the proteins of the different pathways are targetted, so that they form discrete sensory complexes, preventing the different pathways from interacting prematurely. The mechanisms used for maintaining the correct number of pathway complexes in daughter cells on cell division appears to be related to mechanisms used to ensure that the cell divides in the middle, and that each daughter has the correct cytoplasmic compliment on division. These data suggest a much more complex developmental apparatus in bacteria than previously thought. Part of this study will therefore concentrate on identifying the mechanisms involved in organising the formation of the chemosensory pathways, ensuring each daughter cell gets a sensory complex with the right protein complement, so that on division each daughter cell is capable of a chemosensory response. The sensitivity of the E.coli sensory pahway to a few molecules has been suggested to depend on the resetting of the receptors allowing the other receptors to now respond. Receptors from other species are often different from those of E.coli, and the adaptation regions not easily identified. If the same system applies we need to identify related sites on other receptors and this will form part f the project, testing whether a common model can be developed for all bacterial swimming behaviour. Together these data will show which aspects of the E.coli chemosensory model can be extended to other bacterial species, in this case Rhodobacter sphaeroides and whether the organisational mechanisms involved in ensuring daughter cells contain the same DNA and protein are related, allowing a complex developmental model of bacterial growth to be developed.