Identification and characterization of type III secretion system (T3SS) effectors in Edwardsiella tarda

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Aquaculture is a one-billion-dollars business in Canada and it provides about 15,000 full time well-paid jobs in many rural and coastal communities. In 2011, Canada was the fifth largest seafood exporter globally. The aquaculture industry is a significant contributor to the stable and strong Canadian economy; it also provides food security as well as healthy food for the Canadian population. Unfortunately, fish diseases are major challenges to the sustainability and viability of the aquaculture industry. Research in this area is urgently needed not only to support the local industry but also other enterprises around the world. Understanding how pathogens infect and live inside fish cells and tissues, and how they spread throughout the whole fish can lead to the development of adequate control measures and other biotechnological applications. Bacteria secrete proteins into the surrounding environment or host cells to allow them to gain a competitive advantage or to facilitate entry into and survival inside the hosts. At least seven different types of bacterial protein secretion systems, named type I to VII, exist. These systems release disease-causing proteins into their surroundings, directly into host cells, or even to other bacteria found in the same environment. These proteins target specific host proteins and alter their biological functions to gain control of the host. Among the different labs in the world studying bacterial secretion systems, our lab has considerable expertise on both type III and type VI secretion systems (T3SS and T6SS) found in the bacterium Edwardsiella tarda. E. tarda is abundant in water environments and is a common and important pathogen of freshwater and marine fish. The disease properties of E. tarda are due in large part to their T3SS and T6SS.The genome of E. tarda has been decoded. The proposed study seeks to identify and characterize T3SS disease-causing proteins in E. tarda. On average there are 20-30 disease-causing bacterial proteins secreted from a T3SS. E. tarda encodes about 3,700 proteins and 1,000+ of them are classified as potentially new proteins. Our first aim is to identify the T3SS disease-causing proteins from the 1,000+ new proteins. We will use a bioinformatics approach to predict T3SS disease-causing proteins based on their secretion signals. A computing program will be trained for the prediction of T3SS disease-causing proteins. Once we have an adequate program, it will be used to screen the 1,000+ new proteins of E. tarda to shortlist the candidates to about 50. These candidates will be validated using our established protocols for the confirmation of T3SS delivery. The second aim is to characterize the functions of the identified T3SS disease-causing proteins. We would like to find out the targeted host proteins that interact with these bacterial proteins, the physiological functions that these bacterial proteins disrupt or mimic in the host cells, the precise roles of the bacterial proteins at the cellular and molecular levels, and how they collectively and individually contribute to the disease-causing process in fish. With my expertise on bacterial secretion systems and a strong multidisciplinary team, I am confident that we will complete the objectives outlined in this proposal. Potential biotechnological applications include the development of vaccines and novel therapeutics to prevent diseases in fish. This research will not only promote a knowledge-based economy in Canada, but will also have global importance.