Project Number: 8042-31440-001-08-A
Project Type: Cooperative Agreement
Start Date: Mar 15, 2016
End Date: Mar 14, 2019
This project will produce: 1) a treatment for Streptococcus suis, a pathogen that is a significant concern to the US and global pork industry, 2) non-antibiotic, alternative antimicrobials that are highly refractory to resistance development, 3) a more complete understanding of the use(s) and effect(s) of peptidoglycan hydrolases as antimicrobials, and 4) a more complete understanding of the pathophysiology of much-needed non-rodent (porcine) models of infectious disease.
This project will develop pathogen-specific antimicrobials against S. suis that are highly refractory to resistance development. Aim 1) Identify peptidoglycan hydrolase enzyme components and develop triple-acting antimicrobials with three unique lytic activities that target the cell wall and will eradicate S. suis. Aim 2) Characterize triple fusion constructs for three lytic activities and their efficacy against on-the-farm (clinical) isolates of S. suis. Aim 3) Demonstrate triple-acting PGH efficacy in vivo with S. suis infected/colonized pigs. University of MD will perform the initial subcloning, expression and in vitro characterization of the anti-S. suis peptidoglycan hydrolase enzymes. ARS scientists will train the UMD Postdoctoral Fellow in the creation of triple-acting fusion enzymes and pay for the large scale production of the optimal fusion construct for use in pig models (via collaborators at NADC, Ames, Iowa).