Development of Novel Small Molecules as Antibiotic Alternatives for the Control of Rhodococcus Equi in Foals

Scientific Summary: Rhodococcus equi is a leading cause of pneumonia and high mortality in foals worldwide. Currently, R. equi infection in foals is treated with antibiotics, however, they can have harmful side effects and become less effective as resistant strains emerge. There are no available vaccines for the prevention of R. equi infections in foals; thus, it is critical to develop novel antibiotic alternatives to control infection and mitigate antimicrobial resistance risk. Small molecules (SMs) are synthetic or natural compounds with drug-like properties that interact with biological molecules of bacterial cells and can alter their normal functions. SMs will not exert selection pressure on the bacteria during treatment, so they are less likely to develop resistance. In our ongoing experiments, we screened about 1,900 SMs to identify the most potent inhibitors with high efficacy against R. equi. We identified 10 compounds that inhibited 100% of R. equi growth (at 10µM concentration). Out of these, we selected those that showed activity at lower concentrations for further development. Our long-term objective is to develop novel anti-R. equi therapeutics that work alternatively to antibiotics to control the emergence of antibiotic-resistant R. equi strains. We aim to evaluate the selected compounds in vitro and determine their efficacy on R. equi colonization in equine alveolar macrophages and their effect on the macrophage’s immune response. Data obtained from this project will be used to apply for additional extramural funds to develop therapeutics and eventually test in controlled experimental trials. Our study will greatly benefit the equine industry by 1) reducing R. equi infection in foals, directly benefitting horses and producers, 2) reducing reliance on antibiotics and avoiding their side effects, 3) preventing the spread of antibiotic-resistant R. equi, 4) promoting sustainable horse production and health, and 5) reducing economic losses.