Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting virtually any nucleated cell.  It is an opportunistic pathogen that asymptomatically infects ~30% of the world population and can cause severe disease in congenitally infected neonates and immuno-compromised individuals. The pathology associated with toxoplasmosis is a direct result of the parasite-mediated destruction of invaded host cells as the parasite undergoes its asexual lytic cycle. Recently, our laboratory assembled a library of >1,000 small molecules designed to target hydrolases. This screen identified several classes of compounds that dose-dependently inhibited  the ability of the parasite to invade host cells as well as compounds that enhanced  invasion. In this presentation I will describe our efforts to identify and characterize the targets of these lead compounds using active site probes and proteomic methods. These studies demonstrate the utility of small molecules for the study of parasite pathogenesis.

Applying small molecules to the study of parasite pathogenesis

245th National Meeting (2013)

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