In vitro effects of gliotoxin, a natural proteasome inhibitor, on the infectivity and proteolytic activity of Toxoplasma gondii.

We examined the in vitro effect of increasing gliotoxin concentrations on the infectivity of Toxoplasma gondii for NIH-3T3 murine fibroblasts and on Toxoplasma chymotrypsin-like activity, which is specific to the proteasome. Parasite penetration of host cells was not modified by a high gliotoxin concentration (1 microM), but replication was markedly decreased (approximately 50% inhibition by 0.5 microM gliotoxin). Gliotoxin reduced the chymotrypsin-like activity of the Toxoplasma proteasome, but five times less potently than in HeLa cells.