Structural investigations of Adhesin-like proteins in the predatory bacterium Bdellovibrio Bacteriovorus

噬菌蛭弧菌是革兰氏阴性细菌的一种非常有效的捕食者，并进行捕食性的生活方式，即捕食者侵入猎物的周质，随后从内部杀死它们。蛭弧菌能够杀死革兰氏阴性细菌，包括许多耐药病原体，这增加了它被用作“活抗生素”来治疗动物和作物细菌感染的可能性。蛭弧菌的治疗潜力已经通过许多研究来说明，其中已经观察到蛭弧菌在感染的动物模型中杀死肺炎克雷伯氏菌和志贺氏菌。该项目将研究蛭弧菌捕食生命周期中一个目前尚未确定的元素，即蛭弧菌细胞与其猎物的附着。该项目的重点将是捕食性蛋白质，其中包含预测在粘附中发挥作用的结构域。蛭弧菌捕食生命周期的复杂性和特异性反映在其基因组中，因此，其与其他生物的同源性相当低。因此，该项目将利用X射线晶体学和互补技术来获得所提出的粘附素样蛋白的高分辨率结构。从这些结构中收集到的信息将用于揭示分子水平上的猎物附着机制。深入了解多结构域蛭弧菌蛋白和暴露的猎物特征之间的潜在相互作用不仅有助于揭示蛭弧菌生命周期的关键过程，而且还可能打开操纵机制以增加蛭弧菌可以相互作用的猎物范围的可能性。

Bdellovibrio bacteriovorus is an extremely efficient predator of Gram-negative bacteria and carries out a predatory lifestyle which sees the predator invade the prey's periplasm and subsequently kill them from within. Bdellovibrio's ability to kill Gram-negative bacteria, including many antibiotic-resistant pathogens, has raised its possibility of being used as a 'living antibiotic' to treat bacterial infections in animals and crops. The therapeutic potential of Bdellovibrio has been illustrated by a number of studies where it has been observed to kill Klebsiella pneumoniae and Shigella in animal models of infection. This project will study a currently uncharacterised element of Bdellovibrio's predatory lifecycle, the attachment of Bdellovibrio cells to its prey. The key focus of the project will be on predatory proteins which contain domains predicted to play a role in adhesion. The complexity and specificity of Bdellovibrio's predatory lifecycle is reflected within its genome and, as a result of this, its homology to other organisms is fairly low. Therefore, this project will utilise X-ray crystallography and complementary techniques to gain high resolution structures of the proposed adhesin-like proteins. Information gleaned from these structures will then be used to uncover the mechanisms of prey attachment at the molecular level. An in-depth understanding of potential interactions between multi-domain bdellovibrio proteins and exposed prey features will not only help uncover a key process of Bdellovibrio's lifecycle but may also open the possibility of manipulating the mechanism to increase the range of prey with which Bdellovibrio can interact.