Development of Novel Small-Molecule Therapeutics to Control Pathogens Causing Abortion in Mares

Project summary Infectious abortion remains a signi?cant cause of reproductive loss in mares, with Streptococcus equi subsp. zooepidemicus (SEZ) being one of the most common and damaging bacterial pathogens. Increasing antimicrobial resistance and microbiome disruption limit the effectiveness of conventional antibiotic therapies, underscoring the need for alternative strategies. This project aims to develop novel small-molecule (SM) therapeutics as antibiotic-sparing interventions to control SEZ-associated uterine infections. High-throughput screening of 2,500 SMs from diverse libraries identi?ed ten compounds that completely inhibited SEZ growth at low concentrations. The proposed work will further evaluate these candidates for activity against multidrug-resistant strains, bio?lm formation, host cell toxicity, and pathogen colonization in epithelial and macrophage models. Expected outcomes include identi?cation of lead SMs that reduce SEZ virulence while preserving host cell function, establishing a proof-of-concept for innovative, non-antibiotic approaches to prevent equine infectious abortion and improve reproductive outcomes.