Triple-acting Therapeutics For Streptococcus Suis.

Antimicrobials with reduced resistance development are essential to both human and animal health. Antibiotics are commonly used to treat or prevent bacterial diseases, and in food-producing animals to improve feed efficiency.However, antibiotics have numerous unintended or collateral effects, including killing non-target beneficial microbes.These beneficial microbes are the host organism's co-evolved partners and are an essential component of host health. Resistance to antibiotics is a concern in the clinic and on the farm because of the potential for farm-to-clinic resistance transfers. There is increasing pressure to limit antibiotic use in agriculture, and to identify acceptable alternatives to antibiotics for use in food animal production. Increases in antibiotic-resistant Streptococcus suis strains worldwide is presumably due to widespread veterinary use of antibiotics. Notably, peptidoglycan hydrolase (PGH) enzymes for the prevention or treatment of infectious disease have
the potential to reduce or eliminate the need for antibiotic usage. The non-antibiotic nature of PGH antimicrobials has many advantages: 1) near pathogen-specificity helps avoid the concerns associated with broad-spectrum antibiotics; 2) active on multi-drug resistant forms of the pathogen; 3) active on senescent and biofilm forms of the pathogen; 4) non-toxic, non-caustic, and biodegradable; and 5) as enzymes, PGHs can attack the multiple cell wall sites. This proposal will develop pathogen-specific antimicrobials against S. suis that are highly refractory to resistance development (via a strategy that should be applicable to any Gram-positive pathogen).Aim 1. Identify components and develop triple-acting antimicrobials to eradicate S. suis. Aim 2. Characterize triple fusion constructs. Aim 3. Demonstrate triple-acting PGH efficacy in vivo with S. suis infected/colonized pigs.