Studies on the regulation and effector function of a type vi secretion system in edwardsiella tarda

微生物学中的一个关键问题是了解细菌如何在宿主(即动物和人类)中引起疾病。一个重要的机制与细菌向环境中分泌蛋白质的方式有关。到目前为止，对细菌中蛋白质分泌系统的研究已经揭示了至少六种不同类型的蛋白质分泌机制，即I型到VI型。病原体利用这些分泌系统，通常是同时使用多个分泌系统，将致病蛋白质(毒力因子)运送到周围环境或直接进入宿主细胞。VI型分泌系统(T6SS)及其在致病中的关键作用于2006年首次报道，随后被证明存在于许多重要病原体中。我们是世界上为数不多的在T6SS方面拥有相当专业知识的实验室之一，已经积累了大量的初步实验数据。目前的提案旨在详细检查迟缓爱德华氏菌中的T6SS，迟缓爱德华氏菌是一种可以感染人类和水生动物的病原体。由这种生物引起的鱼类死亡已导致全球水产养殖业的严重损失。我们将研究这些T6SS蛋白的调节和效应功能，以探讨这一新的分泌系统的机制。所产生的知识对于理解病原体-宿主相互作用以及生物技术和治疗应用的发展将是重要的。因此，这项研究具有全球意义，并将促进加拿大的知识经济。

A critical problem in microbiology is to understand how bacteria cause diseases in their hosts (i.e. animals and humans). One important mechanism is related to the way bacteria secrete proteins into the environment. To date, studies of protein secretion systems in bacteria have revealed at least six different types of protein secretion machineries, namely types I to VI. Pathogens use these secretion systems, often a number of them simultaneously, to deliver disease-causing proteins (virulence factors) to either the surroundings or directly into host cells. Type VI secretion system (T6SS) and its key role in causing diseases, was first reported in 2006 and subsequently has been shown to be present in many important pathogens. Ours is one of the few laboratories worldwide with considerable expertise on T6SSs, having already accumulated substantial amounts of preliminary experimental data. The current proposal aims to examine in detail the T6SSs in Edwardsiella tarda, a pathogen that can infect both humans and aquatic animals. Fish mortality caused by this organism has led to severe losses in the aquaculture industry worldwide. We will study the regulation and effector functions of these T6SS proteins in order to examine the mechanism of this novel secretion system. Knowledge generated will be important to understand pathogen-host interactions as well as for the development of biotechnological and therapeutics application. This research therefore, is of global importance, and will promote the knowledge-based economy in Canada.