ProTeCT · Proteasome as a target to combat trichomoniasis

Proteasome as a target to combat trichomoniasis

Trichomoniasis caused by Trichomonas vaginalis, a human protozoan parasite, is the most common non-viral sexually transmitted disease in the world. Estimates of the worldwide prevalence of trichomoniasis range from 170-180 million cases annually. Exact numbers are difficult to obtain because the infection is not nationally reportable, and many infections are asymptomatic. In woman the infection can result in serious consequences, such as infertility, pelvic inflammatory disease, premature rupture of placental membranes, preterm delivery and low-birth-weight infants. In men, it can cause epididymitis, prostatitis, and decrease sperm cell motility. Trichomoniasis treatment now relies on two antibiotic drugs – metronidazole and tinidazol but 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 antiparasitic compounds. Proteasomes are multisubunit, energy-dependent, proteolytic complexes that are essential for protein homeostasis in mammalian cells and in protozoa. Unlike mammalian cells parasitic organisms express a single proteasome that is essential for their survival. In a murine model of vaginal trichomonad infection, proteasome inhibitors eliminated or significantly reduced parasite burden upon topical treatment without any apparent adverse effects. These findings validated the proteasome of T. vaginalis as a therapeutic target for development of a novel class of trichomonacidal agents. The overall objective of my project “Proteasome as a target to combat trichomoniasis” is to functionally and structurally characterize proteasome from the parasite Trichomonas vaginalis and develop potent and selective inhibitors as potential chemotherapeutics for trichomoniasis treatment.

Data: CORDIS, © European Union