Fusidic acid is an effective treatment against Toxoplasma gondii and Listeria monocytogenes in vitro, but not in mice.

Fusidic acid is a bacteriostatic antibiotic that inhibits the growth of bacteria by preventing the release of translation elongation factor G (EF-G) from the ribosome. The apicomplexan parasite Toxoplasma gondii has an orthologue of bacterial EF-G that can complement bacteria and is necessary for parasite virulence. Fusidic acid has been shown to be effective in tissue culture against the related pathogen Plasmodium falciparum, and current drug treatments against T. gondii are limited. We therefore investigated the therapeutic value of fusidic acid for T. gondii and found that the drug was effective in tissue culture, but not in a mouse model of infection. To determine whether this trend would occur in another intracellular pathogen that elicits a T helper 1-type immune response, we tested the efficacy of fusidic acid for the bacterium Listeria monocytogenes. Similar to its effects on T. gondii, fusidic acid inhibits the growth of L. monocytogenes in vitro, but not in mice. These findings highlight the necessity of in vivo follow-up studies to validate in vitro drug investigations.

A Toxoplasma gondii mutant highlights the importance of translational regulation in the apicoplast during animal infection.

Toxoplasma gondii is an obligate intracellular parasite of all warm-blooded animals. We previously described a forward genetic screen to identify T. gondii mutants defective in the establishment of a chronic infection. One of the mutants isolated was disrupted in the 3' untranslated region (3'UTR) of an orthologue of bacterial translation elongation factor G (EFG). The mutant does not have a growth defect in tissue culture. Genetic complementation of this mutant with the genomic locus of TgEFG restores virulence in an acute infection mouse model. Epitope tagged TgEFG localized to the apicoplast, via a non-canonical targeting signal, where it functions as an elongation factor for translation in the apicoplast. Comparisons of TgEFG expression constructs with wild-type or mutant 3'UTRs showed that a wild-type 3'UTR is necessary for translation of TgEFG. In tissue culture, the TgEFG transcript is equally abundant in wild-type and mutant parasites; however, during an animal infection, the TgEFG transcript is increased more than threefold in the mutant. These results highlight that in tissue culture, translation in the apicoplast can be diminished, but during an animal infection, translation in the apicoplast must be fully functional.