Structural Fundamentals of Gliding Motility

运动在细胞生命的各个方面都发挥着巨大的作用：逃避伤害，在疾病中殖民宿主，转向食物来源--任何可以通过改变环境获得优势的东西。目前，我们对细胞运动的不同模式的了解存在偏差，例如，我们对游泳(通过旋转的类似尾巴的装置，称为鞭毛)和弹弓爬行(通过称为类型4的抓钩的装置)有很好的分子理解。相反，我们对细菌滑行的工作原理知之甚少，这是一种细胞在表面上滑动的运动方式，没有关于如何实现推进的可见线索。然而，我们确实知道其中涉及的基因，这些基因通常存在于捕食性细菌中，这些专门的有机体利用滑行来猎杀他们的同伴细菌。其中一种捕食者，蜈蚣弧菌(我们在这项研究中选择的生物体)甚至可能被证明在杀死抗生素耐药性细菌方面很有用，而抗生素耐药性细菌是医疗保健中出现的一个问题。对滑行的更好理解将使我们更好地了解捕食者，特别是在它们如何在被称为生物膜的猎物丰富的表面航行方面。除了医疗保健，蜈蚣弧菌和相关的捕食者可能在农作物瘟疫、食品安全、生物污染和水处理方面也有应用。我们在这里的研究旨在验证一个模型，在该模型中，我们围绕一个共同的枢纽拼凑了几个已识别的滑动组件(蛋白质)，旨在将这些组件组织起来，将能量从细胞内输送到细胞外的推进手段。令人兴奋的是，我们的初步研究为每个片段提供了直观的角色，并表明粘连部分与人类细胞的一个已知系统有关--因此可能存在一种进化联系，其中细菌运动是其他系统的祖先。这将由对滑动蛋白质如何组合在一起并相互作用的结构和生化理解推动，这还应该涉及最终告诉我们机械如何工作的几种状态/姿势。我们的研究结果将是“一流的”，因为目前对滑动机械的分子细节一无所知。这项工作将产生广泛的影响--与其他运动模式将有关键的相似和不同之处，这将丰富我们的理解(以及刺激捕食性细菌的直接领域)。

Movement has a huge role to play in all aspects of cellular life: escape from harm, colonizing hosts in disease, moving towards a food source - anything where an advantage can be gained by changing environment. Currently there is a bias in what we know about the different modes of cellular motility, for example we have an excellent molecular understanding of swimming (via a rotary "tail"-like apparatus called the flagellum) and slingshot crawling (via a grappling hook like apparatus called the type 4 pilus). Conversely, we know very little about how bacterial gliding works, a means of motility where the cell slides on a surface with no visible clues as to how propulsion is achieved.We do however know the genes involved, and these are often present in predatory bacteria, specialized organisms that use gliding to hunt and kill their fellow bacteria. One of these predators, Bdellovibrio (our organism of choice for this study) may even prove useful in killing the antibiotic resistant bacteria that are an emerging problem in healthcare. An improved understanding of gliding would lead us to understand predators better, particularly in terms of how they navigate prey-rich surfaces known as biofilms. Besides healthcare, there may be applications for Bdellovibrio and related predators in crop pestilence, food safety, biofouling and water treatment.Our investigation here aims to validate a model in which we have pieced together several identified gliding components (proteins) around a common hub that aims to organize these in conveying energy from inside the cell to a means of propulsion outside the cell. Excitingly, our preliminary studies provide intuitive roles for each of the pieces, and suggest that the adhesive part is related to a known system from human cells - hence there may be an evolutionary link where bacterial movement was the progenitor for other systems. This will be driven by structural and biochemical understanding of how the gliding proteins fit together and interact with one another, which should also involve several states/poses that ultimately tell us how the machinery works.Results from our study will be "first-in-class", as nothing is currently known about the molecular details of the gliding machinery. The work will have broad impact - there will be key similarities and differences to other modes of movement that will enrich our understanding (as well as stimulating the direct field of predatory bacteria).