Chagas disease and leishmaniasis affect 20 million people and lead to more than 50,000 deaths every year. The diseases are caused by infection with the kinetoplastid parasites <i>Trypanosoma cruzi and Leishmania </i>spp<i>.</i> These parasites have similar biology and genomic sequence, suggesting that one drug directed against a conserved target protein could provide a cure for both diseases. However, few targets are known and have been harnessed for drug discovery.  We used unbiased phenotypic screens to enable the identification of small molecules that inhibit pathogen growth by novel mechanisms. We then used chemical genetics with biochemical target validation approaches to validate the parasite proteasome as a promising therapeutic target for treatment of leishmania and Chagas disease. This multi-dimensional approach opens the possibility of developing a single drug for more than one neglected disease indications.

Proteasome inhibitors: A single cure for multiple kinetoplastid diseases

255th National Meeting (2018)

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