Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-233-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2021
End Date: Sep 30, 2026
Objective:
Objective 1: Characterize leptospires circulating in dairy cows to advance the development of efficacious intervention strategies.
Sub-objective 1.1: Detect and classify leptospires circulating in dairy cows.
Sub-objective 1.2: Characterization of recent isolates of pathogenic leptospires.
Sub-objective 1.3: Enhanced bacterin intervention strategies.
Objective 2: Characterize the pathogenesis of DD for the development of more effective intervention strategies.
Sub-objective 2.1: Characterization of Treponema and other pathogens in DD.
Sub-objective 2.2: Development of host immune response to antigens from DD lesions.
Sub-objective 2.3: Development of effective intervention strategies for DD.
Approach:
Leptospirosis and digital dermatitis (DD) are two different diseases caused by two separate groups of bacteria in the Phylum Spirochaetes that have substantial impact on livestock production. Multiple serovars of Leptospira interrogans are the leading cause of acute lethal leptospirosis in humans and domestic animals while serovar Hardjo of L. borgpetersenii is the leading cause of bovine disease, causing reproductive failure and persistent shedding via urine to maintain disease transmission. Current bovine bacterin vaccines are limited in efficacy. To improve on this, Objective 1 will characterize leptospires circulating in dairy cows to advance the development of efficacious intervention strategies. It is first necessary to identify those species and serovars of Leptospira currently circulating in animal populations, as described in subobjective 1.1. Given the importance of L. borgpetersenii to animal disease, subobjective 1.2. will include comparative genomics and proteomics of multiple serovars within Leptospira borgpetersenii to identify conserved pathogenic mechanisms of infection and candidate vaccinogens as potential recombinant subunit vaccines. We hypothesize that efficacy of bacterins can be further improved to provide heterologous protection using growth media that more closely emulates that encountered during host infection, as proposed in subobjective 1.3. Unlike leptospirosis, DD is an infectious polymicrobial skin infection in which Treponema species are found at the invading edge of the lesions. Causing painful ulcerative proliferative and necrotizing lesions on the skin at or near the hooves, DD is a significant cause of lameness in both dairy and feedlot cattle. Aside from lameness being a significant animal welfare issues, DD leads to decreased production, higher treatment costs and premature culling. Objective 2 will characterize the pathogenesis of DD for the development of more effective intervention strategies. Since the etiology of DD is not fully characterized, subobjective 2.1 will use bacterial 16S rRNA gene sequencing to characterize bacterial community of early DD lesions as induced in a sheep model, compare the sheep model to naturally infected bovine DD lesions in order to determine a core consortium of Treponema and other pathogens present. After obtaining isolates representing this core consortium, a defined mixture of Treponema species and other bacterial pathogens will be used to induce lesions in the sheep model. Subobjective 2.2. will then characterize the bovine innate immune responses to Treponema, and how that may affect lesion healing. Since current mitigation strategies use heavy metal, formalin-containing footbaths or topical antibiotics, subobjective 2.3. will evaluate novel alternative antimicrobial compounds for topical treatment of DD lesions. Understanding pathogenic mechanisms used by Spirochetes, specific species causing disease and host-pathogen interactions, are critical for the development of efficacious diagnostics, vaccines, and therapeutics for control of infection in domestic livestock.
