Proteasome as a target to combat trichomoniasis

ended

Trichomoniasis, caused by the protozoan parasite Trichomonas spp., is the most common, non-viral, sexually transmitted infection in the world. Only two closely related antibiotic drugs are approved for its treatment. The accelerating emergence of resistance to current antibiotics and no alternative treatment options pose an increasing threat to public health, resulting in an urgent need for novel effective anti-parasitic compounds. This project focuses on Trichomonas proteasome that is an underexploited enzyme critical for parasite survival. In this proposal, the proteasome will be functionally and structurally characterized. The substrate specificity of each subunit will be determined and fluorescent substrates that can monitor activity of each subunit will be designed. Libraries of proteasome inhibitors will be screened and hit compounds will be analyzed in co-crystallization studies with Tv proteasome. Ultimately, biochemical and structural data will be used to rationally design inhibitors for treatment of trichomoniasis.