Project Number: 8042-31440-001-07-I
Project Type: Interagency Reimbursable Agreement
Start Date: Mar 15, 2016
End Date: Mar 14, 2019
The cell wall degrading peptidoglycan hydrolase enzyme antimicrobials can eradicate both systemic and topical Streptococcus (S.) suis from infected pigs. ARS will eradicate S. suis pathogens by creating novel non-antibiotic antibacterial agents that are based on bacterial cell wall lytic enzymes (i.e. peptidoglycan hydrolases) from bacteriophage (viruses that infect bacteria). Cell wall lytic enzymes (and multi-acting fusion constructs) have been shown to be highly refractory to resistance development in the target pathogen, and therefore we expect that application of these enzymes in food animals will significantly reduce the development and dissemination of antibiotic resistance and protect the farmer, consumer and industry worker from the losses/diseases caused by S. suis.
ARS plans to identify, and purify enzymes lytic for S. suis and show that these enzymes can eradicate porcine isolates of S. suis under (optimal) lab conditions. The highest lytic activity enzymes will be tested pair-wise for antimicrobial synergy. These enzyme antimicrobials degrade the cell wall and thus act externally on the pathogen, conferring numerous advantages over broad range antibiotics by avoiding many [intracellular] bacterial resistance mechanisms toward antibiotics. ARS will then design and create triple-acting fusion enzymes harboring three unique, synergistic streptolytic activities and test these in porcine S. suis infection models via our unfunded collaborators at National Animal Disease Center, Ames, Iowa. These triple-acting fusion proteins will be highly refractory to resistance development, and will be able to treat all forms of S. suis infection including topical, systemic, multi-drug resistant, and biofilms.