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

细菌性蜈蚣弧菌是革兰氏阴性细菌的一种极其有效的捕食者，它的捕食性生活方式是捕食者入侵猎物的周质，然后从内部杀死它们。蜈蚣弧菌能够杀死革兰氏阴性细菌，包括许多抗药性病原体，这增加了它被用作治疗动物和农作物细菌感染的“活抗生素”的可能性。蛭弧菌的治疗潜力已经被一些研究证明，在动物感染模型中观察到它可以杀死肺炎克雷伯氏菌和志贺氏菌。该项目将研究蜈蚣弧菌捕食性生命周期中目前尚未确定的一个因素，即蜈蚣弧菌细胞与其猎物的附着。该项目的重点将放在捕食性蛋白质上，这种蛋白质含有预测在黏附中发挥作用的结构域。蜈蚣弧菌捕食性生命周期的复杂性和特殊性反映在其基因组中，因此，它与其他生物的同源性相当低。因此，该项目将利用X射线结晶学和补充技术来获得所建议的粘附素样蛋白的高分辨率结构。从这些结构中收集的信息将被用来在分子水平上揭示猎物依附的机制。深入了解多结构域蜈蚣弧菌蛋白与暴露的猎物特征之间的潜在相互作用，不仅有助于揭示蜈蚣弧菌生命周期的关键过程，还可能为操纵该机制以扩大蜈蚣弧菌与之相互作用的猎物范围提供可能。

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.