Project Number: 3625-32000-081-00
Project Type: Appropriated

Start Date: Nov 01, 2006
End Date: Oct 31, 2011

Objective:
This research is designed to obtain information leading to a detailed understanding of how two groups of spirochetes interact with the host leading to tissue colonization, infection, and the manifestation of disease. The overarching goal of this project is to identify specific steps during bacterial infection that can be disrupted or otherwise altered to gain protective immunity in livestock. To achieve this goal we will use a combination of genetic, cellular, and immunological approaches to analyze how the host responds to the presence of bacteria, identify genes expressed by bacteria during interactions with host cells, and test protein products for their potential to induce protective immunity enabling animals to resist infection. This project has three specific objectives: (1) Characterize host-pathogen interactions to identify pathogenic mechanisms and detect host cell changes during experimental infection. (2) Genetic characterization of pathogenic spirochetes. (3) Evaluation of immune response to spirochete antigens.

Approach:
Objective 1 will use in vitro methods to detail various aspects of the host response to spirochete infection using a controlled environment. These studies will help develop assay techniques and identify key markers that will be used to evaluate the host response during infection of whole animals, during fulfillment of Objective 3. Objective 2 will use a genomics-based approach to identify bacterial antigens, adhesins, and potential virulence factors to detail the processes by which pathogenic spirochetes establish infections, invade tissue, and evade clearance mechanisms of the host. Objective 3 brings research under the first two objectives together to study host-parasite interactions in animals, with the goal of identifying antigens that induce protective immunity (Leptospira) or develop model systems for future whole-animal studies (PDD spirochetes). BSL-2; Recertified 10/15/08 (IBC-#0242) BSL-2; Recertified 11/24/07 (IBC-#0256) BSL-2; Recertified 08/03/08 (IBC#-0262) BSL-Exempt; Recertified 08/03/08 (IBC#-0263) BSL-Exempt; Recertified 10/15/08 (IBC-#0195)