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Transcript-level responses of Plasmodium falciparum to thiostrepton. | LitMetric

Transcript-level responses of Plasmodium falciparum to thiostrepton.

Mol Biochem Parasitol

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, Cambridgeshire CB2 1QW, United Kingdom.

Published: September 2011

AI Article Synopsis

  • The study challenges the traditional understanding of how the antibiotic thiostrepton kills malaria parasites by suggesting it may also affect mitochondrial protein synthesis, not just apicoplast function.
  • Researchers found that thiostrepton-treatment resulted in delayed changes in gene expression in the malaria parasite Plasmodium falciparum, indicating complex cellular responses.
  • A few specific genes related to mitochondrial functions were regulated differently, hinting at possible communication between the mitochondria and nucleus in the parasite.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.molbiopara.2011.05.004DOI Listing

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