The apicoplast of Plasmodium falciparum is translationally active

Abstract

SummaryApicoplast, the plastid-like organelle of apicomplexan parasites, has generated interest as a putative drug target. Although transcripts for genes encoded by the 35 kb circular plastid DNA have been detected, the actual presence of their protein products has only been postulated. We provide evidence for translation of the tufA gene encoded by the Plasmodium falciparum apicoplast genome. Translation elongation factor Tu (EF-Tu), the product of tufA , was localized within the organelle. TufA was found to express maximally in the trophozoite stage of the intraerythrocytic cycle. Additionally, the drug thiostrepton that has a binding site in apicoplast LSU rRNA, reduced P. falciparum apicoplast EF-Tu levels thus strengthening the view that translation in the apicoplast is the site of action of this drug.

Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs

“…It has not been reported whether male gametocytes are more sensitive to oxidative damage than female gametocytes; however, this hypothesis could be supported by our observation that endoperoxides were inhibitory in the exflagellation assay and not in the female activation assay (Table 1). Thiostrepton is an antimalarial antibiotic targeting apicoplast protein synthesis (40) and the Plasmodium proteasome, and it has been reported to be active against early-stage gametocytes (41). Here we showed activity against both male and female gametocytes, as expected for a compound targeting such universal biological pathways.…”

Inhibition of Protein Synthesis and Malaria Parasite Development by Drug Targeting of Methionyl-tRNA Synthetases

“…Almost 60% of encoded proteins appear to be unique to the parasite, reflecting great evolutionary distance between the parasite and the genomes of known eukaryotes (3). The malaria parasite (and the related apicomplexan Toxoplasma gondii) has three translationally active compartments, i.e., cytoplasm, apicoplasts, and mitochondria (4)(5)(6)(7)(8). All malaria parasite proteins involved in the protein synthesis machinery are encoded by the nuclear genome.…”

“…All malaria parasite proteins involved in the protein synthesis machinery are encoded by the nuclear genome. Either these proteins are transported to target organelles or their modified/activated substrates are transported across the organelles to perform required functions (4)(5)(6)(7)(8)(9). The primary enzymes responsible for translating genetic code into polypeptide chains are aminoacyl-tRNA synthetases (aaRSs).…”

Translation in Mitochondria and Apicoplasts of Apicomplexan Parasites

“…The tufA gene encoding EF-Tu is found in the apicoplast of all apicomplexan parasites (Chaubey et al 2005) while mitochondrial EF-Tu is nuclear-encoded (Pino et al 2010). Nuclear-encoded nucleotide exchange factor EF-Ts has been shown to be targeted to the apicoplast in P. falciparum and its ability to mediate GDP-GTP exchange on apicoplast EF-Tu has been demonstrated (Biswas et al 2011).…”

“…Apicomplexan parasites such as Plasmodium and Toxoplasma have an A + T-rich (86.9 % and 78.4 % A + T, respectively), 35 kb circular apicoplast genome that is actively translated (Chaubey et al 2005). Although the universal genetic code is followed in the cytosol and mitochondrion, there is evidence that the stop codon UGA is recognized as tryptophan within specific ORFs in the apicoplast of Neospora, Toxoplasma and Plasmodium (Lang-Unnasch and Aiello 1999;Wilson 2002).…”