Function of the Bacterial Cytoskeleton in the Pathogenicity of Salmonella

沙门氏菌是具有全球医学重要性的细菌，可导致从胃肠炎到伤寒等多种人类疾病。了解沙门氏菌致病的机制可能有助于开发抗击疾病的新型药物和疫苗。沙门氏菌拥有大量武器或毒力因子，使其能够致病。然而，这些复杂的大分子毒力结构的组装仍有待充分阐明。可以想象，可能需要一个支架或细胞骨架来提供组装这些结构的支持和组织。该建议基于我们尚未发表的关于沙门氏菌mre操纵子的初步数据，该操纵子包含七个基因，其中第一个mreB编码在哺乳动物细胞中发现的细胞骨架蛋白肌动蛋白的同源物。我们已经构建了mre操纵子突变体，并将确定这些突变对重要大分子毒力因子功能的影响。我们将研究MRE操纵子编码的蛋白质如何在沙门氏菌中发挥作用，并调节它们与宿主组织的相互作用。这一方法将为细菌细胞骨架对毒力的贡献提供重要的见解。

Salmonella are bacteria of global medical importance and cause a broad range of diseases in humans from gastroenteritis to typhoid fever. Understanding the mechanisms by which salmonella cause disease may help in developing novel drugs and vaccines to combat disease.Salmonella possess an armoury of weapons or virulence factors which enable them to cause disease. However the assembly of these complex macromolecular virulence structures remains to be fully elucidated. It is conceivable that a scaffold or cytoskeleton may be required to provide support and organisation for assembling these structures.The proposal builds upon our unpublished preliminary data on the Salmonella Mre operon which contains seven genes, the first of which mreB encodes a homologue of the cytoskeletal protein actin found in mammalian cells. We have constructed Mre operon mutants and will determine the impact of these mutations on the functionality of important macromolecular virulence factors. We will be studying how the Mre operon encoded proteins function within Salmonella, and modulate their interactions with host tissues. This approach will provide important insights in the contribution of the bacterial cytoskeleton to virulence.