UC San Diego

Tritrichomonas foetus is the causative agent in intestinal feline infections. The current treatment, ronidazole (Rz), is the only 5-nitroimidazole (5-NI) drug shown to have an effect against T. foetus; however it has been observed to be less than 70% effective. We, therefore, aimed to develop upon compounds that had a more potent efficacy against clinically isolated strains of T. foetus. In doing so, we screened a library of 630 5-NI compounds, 52 (8%) were found to be more effective than Rz in multiple strains in vitro. We developed a novel murine model of T. foetus infection to expand upon the efficacy of the compounds under in vivo conditions. Elucidating various parameters, antibiotic conditioning was observed to be an effective method in generating a sustainable T. foetus colonization. The infection was characterized by a high population of T. foetus within the cecum as well as histological evidence showing a host inflammatory response. Selected compounds which showed superior activity in vitro; were examined in our newly established in vivo model, providing a useful tool in understanding the pharmacokinetics within the host. One compound demonstrated effective capabilities in reducing and inhibiting the growth of T. foetus. This compound can be our lead for further development as a potential chemotherapeutic drug against intestinal T. foetus infection