Abstract
Apicomplexans are an important group of pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. These single-celled eukaryotic parasites evolved from photosynthetic algae. A remnant chloroplast, called the apicoplast, is a telltale hold-over from this more benign past in the ocean. The apicoplast is essential for parasite growth and development and therefore a potential target for drug therapy. The fact that humans and animals lack chloroplasts suggests that using approaches to target the apicoplast may provide parasite specificity. What are the critical functions of the apicoplast that should be targeted? In addition to the obvious medical relevance this question has broader biological implications. Why do organisms maintain an ancient symbiotic relationship when the initial rationale for this relationship has fallen by the evolutionary wayside? A new study by Yeh and DeRisi provides important clues. Their work demonstrates that antibiotic-induced loss of the apicoplast in cultured malaria parasites can be chemically rescued by providing isopentenyl-pyrophosphate (IPP) in the medium. IPP is generated by the apicoplast resident isoprenoid biosynthesis pathway and is apparently the one apicoplast metabolite that the parasite cannot live without in the red blood cell. This finding could be of great importance for the development of drugs and vaccines. The ability to produce and maintain parasite lines that lack the apicoplast also offers exciting experimental possibilities for the future.
Highlights
Apicomplexans are a phylum of protists that live as intracellular parasites in a tremendous variety of vertebrate and invertebrate animals
When apicomplexans abandoned photosynthesis instead of producing metabolites for free, the apicoplast had to be fed with energy and carbon precursors from the cytoplasm of the parasite [15,16]
Subsequent genetic studies showed that loss of apicoplast fatty acid synthesis is lethal in Toxoplasma and the liver stages of Plasmodium, but that it can be tolerated in the clinically most important red blood cell (RBC) phase of malaria [26,27,28]
Summary
Apicomplexans are an important group of pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis These single-celled eukaryotic parasites evolved from photosynthetic algae. IPP is generated by the apicoplast resident isoprenoid biosynthesis pathway and is apparently the one apicoplast metabolite that the parasite cannot live without in the red blood cell This finding could be of great importance for the development of drugs and vaccines. Many of the chromalveolate kin of the apicomplexans are algae that harvest sunlight by photosynthesis, including kelps, diatoms, dinoflagellates, and haptophytes They are responsible for the bulk of primary production and carbon fixation in the ocean. Apicomplexans are unique in that they largely maintained the plastid despite the fact that they are no longer photosynthetic (a few, such as Cryptosporidium, have lost the organelle [8,9])
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