Short communicationTranscript-level responses of Plasmodium falciparum to thiostrepton

The antimalarial activity of the antibiotic thiostrepton has long been attributed to inhibition of apicoplast protein synthesis through binding of apicoplast ribosomal RNA. However, the kinetics of parasite death upon thiostrepton treatment differ from those seen for other inhibitors of apicoplast housekeeping functions. We have analysed global changes in gene expression of the malaria parasite, Plasmodium falciparum, in an attempt to shed light on the responses of the parasite to this drug. Our results indicate a delay in gene expression profiles of thiostrepton-treated parasites. A small number of genes appear to be regulated outside of this trend; our data suggest a response from genes encoding components of the mitochondrial translational machinery, while little response is seen from genes encoding apicoplast-targeted proteins. Our findings are consistent with an effect of thiostrepton on mitochondrial protein synthesis, and thus warrant a re-evaluation of the target of thiostrepton in Plasmodium. They also provide some suggestion of mitochondrion-nucleus signalling in the parasite.

Treatment of Plasmodium falciparum with thiostrepton caused a delay in parasite gene expression profiles and perturbation of the mitochondrion.153Highlights► Treatment with thiostrepton caused large changes in gene expression in Plasmodium falciparum. ► Microarray analysis indicated a delay in the gene expression profiles of thiostrepton-treated parasites. ► Genes encoding mitochondrially targeted proteins showed altered expression outside of this trend, suggesting perturbation of mitochondrial function and mitochondrion-nucleus signalling in thiostrepton-treated parasites.