Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-223-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2016
End Date: Sep 30, 2021
Objective:
These studies are focused on developing an understanding of how Leptospira and Treponema species interact with their hosts to establish colonization, infection, and clinical disease. A combination of genomic, proteomic and immunological methodologies will be used to analyze how the host responds to infection and how bacteria respond to the host, with the long-term goal of identifying pathways that can be targeted to alter disease outcomes or exploited to induce protective immunity.
Objective 1. Identify and characterize the Leptospira and Treponema sp. circulating in livestock.
Subobjective l.1 - Determine prevalence of leptospires circulating in local bovine herds.
Subobjective l.2 - Characterize clonal isolates of Treponema from bovine digital dermatitis at the phenotypic, genomic and proteomic level.
Objective 2. Develop animal models that will mimic infection, facilitate characterization of interactions between host and pathogen, and allow development of assays that will accurately identify infected individuals.
Subobjective 2.1 - Characterize urinary immunoglobulin from reservoir hosts of leptospirosis.
Subobjective 2.2 - Characterize the cellular immune response of reservoir hosts of leptospirosis.
Subobjective 2.3 - Characterize and refine an ovine model of bovine digital dermatitis.
Objective 3. Characterize spirochete antigens including those that are differentially expressed during infection.
Subobjective 3.1 - Identification and characterization of leptospiral proteins that are expressed in response to mammalian host signals.
Subobjective 3.2 - Characterize host humoral responses to outer membrane protein antigens derived from bacteria associated with digital dermatitis.
Approach:
Objective 1: This objective seeks to identify and characterize species of Leptospira and Treponema sp. circulating in livestock. Studies will be conducted to determine the prevalence of leptospires circulating in local bovine herds (Sub-objective 1.1); and to characterize clonal isolates of Treponema from bovine digital dermatitis at the phenotypic, genomic and proteomic levels (Sub-objective 1.2). We expect these studies to determine if serovars of leptospires currently circulating in bovine populations of the Mid-West have changed over the last 20 years and to demonstrate that different phylotypes of Treponema derived from bovine digital dermatitis have unique genomic, proteomic and virulence factors.
Objective 2: Development of animal models that mimic infection will facilitate characterization of interactions between host and pathogen, and allow development of assays that will accurately identify infected individuals. Urinary immunoglobulins from reservoir hosts of leptospirosis will be collected and characterized (Sub-objective 2.1); the cellular immune response of reservoir hosts of leptospirosis will also be characterized (Sub-objective 2.2); and an ovine model of bovine digital dermatitis will be further characterized and refined (Sub-objective 2.3). We will also evaluate immune activation pathways in a reservoir host model of leptospirosis using the inbred Fisher 344 rat. Studies conducted will advance the use of sheep as a ruminant model to understand the pathogenic mechanisms and involvement of treponemes in digital dermatitis.
Objective 3: Characterize spirochete antigens including those that are differentially expressed during infection. Studies will be conducted to identify and characterize leptospiral proteins that are expressed in response to mammalian host signals (Sub-objective 3.1) and to characterize host humoral responses to outer membrane protein antigens derived from bacteria associated with digital dermatitis (Sub-objective 3.2).
