Apicoplasts

Clindamycin, a lincosamide derivative, inhibits protein biosynthesis within a unique organelle of the parasite, termed apicoplast. Its mode of action is similar to that of spiramycin. 

Some organisms, notably parasites, have organelles , which appear to be relics of chloroplasts but have no photosynthetic capacity. They are called apicoplasts but are probably not the origin of chloroplasts. Also note that a feature of symbiosis is that genes that are no longer required can be selectively lost as was probably the case in the example of loss from bacteria on becoming mitochondria (mentioned above). 

A number of antibiotics in addition to the folate antagonists and sulfonamides are modestly active antimalarials. The antibiotics that are bacterial protein synthesis inhibitors appear to act against malaria parasites by inhibiting protein synthesis in a plasmodial prokaryote-like organelle, the apicoplast. None of the antibiotics should be used as single agents in the treatment of malaria because their action is much slower than that of standard antimalarials. 

C. parvum is a protist related to the apicomplexans P. falciparum and Toxoplasma. P. falciparum and T gondii possess the apicoplast organelle, a remnant plastid acquired by secondary symbiosis. It has been shown that the I gondii apicoplast is segregated into daughter cells by microtubules of mitotic spindle poles (Striepen et al. 2000). As the apicoplast is in contact with the mitochondrion, it has been hypothesized that mitochondrial inheritance... 

C. parvum is the apicomplexan which lacks an apicoplast, direct contact between the mitosomes and mitotic spindle might be expected. There is still no information available on the movement and segregation of the mitosomes of... 

The machinery mediating this process was shown to be of an ISC type. Phylogenetic analyses indicate that the mitochondrial ISC machinery was inherited from the proteobacterial endosymbiont, which is consistent with the proposed origin of mitochondria (Tachezy et al. 2001). Components of the SUF system were found in plastids and in the apicoplast of apicomplexan such as P. falciparum (Wilson et al. 2003). The SUF machinery was most likely inherited from cyanobacteria, the ancestors of plastids (Tachezy et al. 2001). Entamoebids and related protists are the only eukaryotes which acquired components of the NIF system ( et al. 2004 van der Giezen et al. 

Cai X, Fuller AL, McDougald LR, Zhu G (2003) Apicoplast genome of the coccidian Eime-ria tenella. Gene 321 39-46... 

From the chloroquine microarray data, we found that trypto-phanyl-tRNA synthetase production in the apicoplast is upregu-lated. Others have hypothesized that resistant P. falciparum parasites have a mechanism for releasing chloroquine via an efflux process (26, 27). We prove in this work that the upregulated tryp-tophanyl-tRNA synthetase production in the apicoplast suggests that this efflux process may have been made possible (caused) by the apicoplast, the mini bacterium living inside the malaria parasite. We hypothesize that when our results are experimentally proved, in particular for the case of chloroquine, our findings may lead to better and more cost-effective agents for eradication of the parasite from the human blood stream. 

Therefore, that tryptophanyl-tRNA synthetase production in the apicoplast is upregulated (in the chloroquine-induced microarray data) may suggest that this efflux process was made possible (caused) by the apicoplast, the mini bacterium living inside the malaria parasite. Ralph et al. (45) state that it is not yet clear what the key function of the apicoplast is but the organelle is clearly indispensable. Curiously though, parasites cured of their apico-plasts do not die immediately. Rather, they fail to invade new host cells successfully. This suggests that apicoplasts provide some component essential to invasion and or [sic] establishment of the para-sitophorous vacuole in the host cell (46, 47). 

Thus a combination of chloroquine with the agents that cured P. falciparum of its apicoplast may be helpful in preventing the parasite from invading new host cells, and this combination may also kill the parasite, because it could not then flux out accumulated chloroquine in its digestive food vacuole. 

Dahl EL, Shock JL, Shenai BR et al (2006) Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother 50(9) 3124-3131... 

Ralph SA, D Ombrain MC, McFadden GI (2001) The apicoplast as an antimalarial drug target. Drug Resist Updat 4 145-151... 

Maeda T, Saito T, Harb OS et al (2009) Pyruvate kinase type -II isozyme in Plasmodium falciparum localizes to the apicoplast. Parasitol Int 58(1) 101-105... 

Vollmer M, Thomsen N, Wiek S, Seeber F (2001) Apicomplexan parasites possess distinct nuclear-encoded, but apicoplast-localized, plant-type ferredoxin-NADP(+) reductase and ferredoxin. J Biol Chem 276 5483-5490... 

In plants, some steps of the biosynthesis of tetrahy-drofolate, biotin, and lipoate proceed in mitochondria (7, 15), whereas the biosynthesis of vitamin B2 is operative in plastids (67). In apicomplexan protozoa, enzymes in mitochondria, in the apicoplast (an organelle that is believed to have a common evolutionary origin with chloroplasts) and in the cytoplasmic... 

Ralph SA, van Dooren GG, Waller RF, Crawford MJ, Fraunholz, MJ, Foth, BJ, Tonkin, CJ, Roos, DS and McFadden, GI. Tropical infectious diseases metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat. Rev. Microbiol. 2004 2 203-216. 

RNA polymerase. This work eventually led to the identification of the apicoplast a few years later. Doing a great deal of manual sequencing and learning how to use computer programs to collect and analyze sequence data were skills that would prove useful later. 

In apicoplast FA biosynthesis, the main carbon substrate is acetyl-coenzyme A (acetyl-CoA) generated from acetate by the action of acetyl-CoA synthase or from pyruvate by the pyruvate dehydrogenase (PDH) complex. Within the plastid, pyruvate is formed by the action of... 

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