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，向食物来源移动-任何可以通过改变环境获得优势的事情。目前，我们对细胞运动的不同模式的了解存在偏见，例如，我们对游泳（通过称为鞭毛的旋转“尾巴”状装置）和弹弓爬行（通过称为4型菌毛的抓钩状装置）有很好的分子理解。相反，我们对细菌滑行的原理知之甚少。细菌滑行是一种运动方式，细胞在表面滑动，没有明显的线索来说明如何实现推进力。然而，我们确实知道相关的基因，这些基因通常存在于捕食性细菌中，这些细菌是利用滑行来捕食和杀死其他细菌的特殊生物。其中一种捕食者，蛭弧菌（我们这项研究的选择生物）甚至可能被证明在杀死抗生素耐药性细菌方面是有用的，这是医疗保健中的一个新问题。对滑翔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导航方面。除了医疗保健，蛭弧菌和相关的捕食者在农作物瘟疫，食品安全，生物污损和水处理方面也有应用。我们的研究旨在验证一个模型，在这个模型中，我们将几个已识别的滑行组分（蛋白质）拼凑在一起，围绕一个共同的枢纽，旨在组织这些将能量从细胞内传递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作用，并表明粘附部分与人类细胞的已知系统有关-因此可能存在进化联系，其中细菌运动是其他系统的祖先。这将是由结构和生物化学的理解如何滑动蛋白装配在一起，并与彼此相互作用，这也应该涉及到几个状态/姿势，最终告诉我们如何机器工作，从我们的研究结果将是“一流的”，因为没有什么是目前所知的分子细节的滑动机器。这项工作将产生广泛的影响-将有关键的相似性和差异，以其他模式的运动，这将丰富我们的理解（以及刺激直接领域的捕食性细菌）。

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).