Plasmodium lophurae

The first attempt to prepare an azaindole as an azalog of biologically active compounds appears to have been made by Bernstein et al. They synthesized 6-amino-2,3-diphenyl-7-azaindole and tested it for antimalarial activity against Plasmodium lophurae. It showed little activity. 

Ribosomes of Plasmodium knowlesi were isolated and characterized recently by Sherman et al. 21 These ribosomes sedimented in the 80S range and could be dissociated into 60S and 40S subparticles. The ribosomal RNA had a low % G+C of 37% and had sizes of 24.2S and 16.6S.22 The ribosomes demonstrated high activity in poly(IJ)-directed synthesis of polyphenylalanine and were strongly inhibited by 10 4m of nucleocidin, chlortetracycline, ethidium, puromycin, cycloheximide or berenil.23 Similar studies have been also carried out on Plasmodium lophurae, and similar profile of drug sensitivities were demonstrated.24 Most of the well-known antimalarial drugs tested showed no significant inhibitory activity in this in vitro assay. 

In 1968, my graduate student Charles Walsh and I addressed the following question What are the pyrimidine sources for nucleic acid synthesis by Plasmodium lophurae We found the parasite synthesized pyrimidines de novo (Walsh and Sherman, 1968b). The evidence for a de novo synthesis was the presence of the key enzymes, thymidylate synthetase and oroti-dine-5-monophosphate pyrophosphorylase, as well as the demonstration of the incorporation of 14C-bicarbonate into cytosine, uracil and thymine. Finding a de novo pathway for the synthesis of pyrimidines by the malaria parasite would, in the next three decades, provide a biochemical basis for the mechanism of action of anti-folate anti-malarials as well as contributing to an understanding of the unique properties of the malaria parasite mitochondrion. 

Most of the work on membrane transport with malaria parasites prior to 1990 concerned itself with studies of bird, murine and monkey plasmodia (Plasmodium lophurae, P. berghei and P. knowlesi) and this was summarized some 20 years ago (Sherman, 1979,1988). With the successful in vitro culture of P. falciparum, membrane-transport phenomena of malaria-infected red cells and free parasites have concerned themselves principally with this species and this too has been the subject of periodic review (e.g. see Kirk s tour de force, 2001). 

Bennett, T. P., and Trager, W. (1967). Pantothenic acid metabolism during avian malaria infection Pantothenate kinase activity in duck erythrocytes and in Plasmodium lophurae. ]. Protozool. 14, 214-216. 

Booden, T., and Hull, R. W. (1973). Nucleic acid precursor synthesis by Plasmodium lophurae parasitizing chicken erythrocytes. Exp. Parasitol. 34,220-228. 

Brohn, F. H., and Trager, W. (1975). Coenzyme A requirement of malaria parasites Enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae. Proc. Natl. Acad. Sci. USA 72, 2456-2458. 

Coggeshall, L. T. (1938b). Plasmodium lophurae, a new species of malaria pathogenic for the domestic fowl. Am. J. Hyg. 27,615-618. 

Hewitt, R. (1942). Studies on the host relationships of untreated infection with Plasmodium lophurae in ducks. American ]. of Hygiene 36, 6-42. 

Kilejian, A. (1975). Circular mitochondrial DNA from the avian malarial parasite Plasmodium lophurae. Biochim. Bicrphys. Acta 390,276-284. 

Kilejian, A., Chen, S., and Sloma, A. (1985). The biosynthesis of the histidine-rich protein of Plasmodium lophurae and the cloning of its gene in Escherichia coli. Mol. Biochem. Parasitol. 14, 1-10. 

Kovic, M., and Zeuthen, E. (1967). Malarial periodicity and body temperature. An experimental study of Plasmodium lophurae in chicken embryos. C. R. Trav. Lab. Carlsberg 36, 209-223. 

Margossian, S. S., McPhie, P., Howard, R. J., Coligan, J. E., and Slayter, H. S. (1990). Physical characterization of histidine-rich protein from Plasmodium lophurae. Biochim. Biophys. Acta 1038,330-337. 

McGhee, R., and Trager, W. (1950). The cultivation of Plasmodium lophurae in vitro in chicken erythrocyte suspensions and the effects of some constituents of the culture medium upon its growth and reproduction. ]. Parasitol. 36,123-127. 

McGhee, R. B. (1953b). The infection by Plasmodium lophurae of duck erythrocytes in the chicken embryo. ]. Exp. Med. 97,773-782. 

Platzer, E. G. (1972). Metabolism of tetrahydrofolate in Plasmodium lophurae and duckling erythrocytes. Trans. N. Y. Acad. Sci. 34, 200-207. 

Platzer, E. G. (1977). Subcellular distribution of serine hydroxymethyltransferase in Plasmodium lophurae. Life Sci. 20,1417-1424. 

Ravetch, J. V., Feder, R., Pavlovec, A., and Blobel, G. (1984). Primary structure and genomic organization of the histidine-rich protein of the malaria parasite Plasmodium lophurae. Nature 312, 616-620. 

Schimandle, C. M., and Sherman, I. W. (1983). Characterization of adenosine deaminase from the malarial parasite, Plasmodium lophurae, and its host cell, the duckling erythrocyte. Biochem. Pharmacol. 32,115-122. 

Sherman, I. W. (1961). Molecular heterogeneity of lactic dehydrogenase in avian malaria (Plasmodium lophurae). J. Exp. Med. 114,1049-1062. 

Sherman, I. W. (1965). Glucose-6-phosphate dehydrogenase and reduced glutathione in malaria-infected erythrocytes (Plasmodium lophurae and P. berghei).. Protozool. 12, 394-396. 

Sherman, I. W. (1981). Plasmodium lophurae Protective immunogenicity of the histidine-rich protein Exp. Parasitol. 52,292-295. 

Sherman, I. W., and Mudd, J. B. (1966). Malaria infection (Plasmodium lophurae) Changes in free amino acids. Science 154,287-289. 

Sherman, I. W., and Tanigoshi, L. (1974). Glucose transport in the malarial (Plasmodium lophurae) infected erythrocyte.. Protozool. 21, 603-607. 

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