The antibiotic monensin causes cell cycle disruption of Toxoplasma gondii mediated through the DNA repair enzyme TgMSH-1.

ABSTRACT: Monensin is a polyether ionophore antibiotic that is widely used in the control of coccidia in animals. Despite its significance in veterinary medicine, little is known about its mode of action and potential mechanisms of resistance in coccidian parasites. Here we show that monensin causes accumulation of the coccidian Toxoplasma gondii at an apparent late-S-phase cell cycle checkpoint. In addition, experiments utilizing a monensin-resistant T. gondii mutant show that this effect of monensin is dependent on the function of a mitochondrial homologue of the MutS DNA damage repair enzyme (TgMSH-1). Furthermore, the same TgMSH-1-dependent cell cycle disruption is observed with the antiparasitic ionophore salinomycin and the DNA alkylating agent methyl nitrosourea. Our results suggest a novel m

SUBMITTER: Lavine MD 

PROVIDER: S-EPMC3028789 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature