Anticancer proteasome inhibitors are detrimental to the growth of Toxoplasma gondii in vitro

Objective Toxoplasma gondii is a globally widespread intracellular protozoan that infects an estimated 25% of the world's human population. There is currently no cure for chronic toxoplasmosis, and treatments for acute infection often cause harmful side effects. Here, we used well-established growth assays to evaluate the anti-toxoplasmic effects of three FDA-approved anticancer proteasome inhibitors, bortezomib, carfilzomib, and ixazomib, on Toxoplasma growth in vitro. Results We found that treatment of Toxoplasma with bortezomib, carfilzomib, and ixazomib inhibits parasite growth with IC ₅₀ values of 204.9 nM, 116.5 nM, and 7.05 µM, respectively. Additionally, bortezomib and ixazomib impair parasite replication 24h post-infection and cause asynchronous cell division and the formation of aberrant parasites. Our study provides evidence in favor of further investigation of these anticancer drugs for in vivo efficacy and their repurposing for the treatment of toxoplasmosis.