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

乳酸菌弧菌是一种极其有效的革兰氏阴性菌捕食者，它的捕食方式是侵入猎物的外周质，然后从内部杀死它们。蛭弧菌能够杀死革兰氏阴性菌，包括许多耐抗生素病原体，这提高了它被用作治疗动物和作物细菌感染的“活抗生素”的可能性。许多研究表明，在动物感染模型中，蛭弧菌可以杀死肺炎克雷伯菌和志贺氏菌，说明了蛭弧菌的治疗潜力。该项目将研究蛭弧菌掠食性生命周期中目前尚未确定的元素，即蛭弧菌细胞与猎物的附着。该项目的重点将放在掠夺性蛋白质上，这些蛋白质含有预测在粘附中起作用的结构域。蛭弧菌掠食性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黏附蛋白的高分辨率结构。从这些结构中收集的信息将用于揭示猎物在分子水平上的附着机制。深入了解多结构域蛭形弧菌蛋白与暴露猎物特征之间的潜在相互作用，不仅有助于揭示蛭形弧菌生命周期的关键过程，而且可能为操纵该机制增加蛭形弧菌可以相互作用的猎物范围提供可能性。

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.