Nutritional Requirements of <i>Plasmodium falciparum</i> in Culture. I. Exogenously Supplied Dialyzable Components Necessary for Continuous Growth

Divo, Alan A.; Geary, Timothy G.; Davis, Nella L.; Jensen, James B.

doi:10.1111/j.1550-7408.1985.tb03013.x

Cited by 207 publications

(190 citation statements)

References 45 publications

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“…Increases of glutamine influx and glutamate formation were observed in erythrocytes infected with a human malaria parasite, P. falciparum [25]. Because human erythrocytes are essentially impermeable to glutamate [3], extracellular glutamine might be transported into the cells and converted into glutamate through glutaminase, which is present in P. falciparuminfected erythrocytes [30]. These previous observations and the results of present study indicate that glutamate is an additional energy source for B. gibsoni.…”

Section: Discussionsupporting

confidence: 70%

The Cause of the Predilection of Babesia gibsoni for Reticulocytes.

Yamasaki

Otsuka

Yamato

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. This study was conducted to determine why Babesia gibsoni replicates well in reticulocytes. First, B. gibsoni was cultivated in resealed erythrocyte ghosts loaded with either erythrocyte or reticulocyte lysate, and in reticulocyte ghosts loaded with either erythrocyte or reticulocyte lysate. The parasites multiplied well in the erythrocyte or reticulocyte ghosts loaded with reticulocyte lysate compared to the other resealed cells loaded with erythrocyte lysate. Second, the parasites were cultivated in erythrocytes in culture medium supplemented with either erythrocyte or reticulocyte lysate. The parasites multiplied better in reticulocyte lysate-containing cultures than in erythrocyte lysate-containing cultures. Finally, the parasites were cultivated in erythrocytes in culture medium supplemented with glutamate, aspartate, asparagine, glycine, isoleucine, proline, taurine or GSH, which were present in higher concentrations in reticulocytes than in erythrocytes. Supplementation of the culture medium with glutamate and GSH resulted in enhancement of the multiplication of the parasites, while the other amino acids did not enhance the multiplication. These results indicated that the high levels of the multiplication of B. gibsoni in reticulocytes are partly due to the high concentrations of glutamate and GSH in reticulocytes. We previously reported that Babesia gibsoni parasites invade and multiply better in reticulocytes than in mature cells in vitro [16]. It has also been reported that several species of Babesia parasites such as B. rodhaini, B. microti [20] and B. canis [4], have a predilection for reticulocytes, while B. hylomisci prefers mature erythrocytes to reticulocytes for multiplication [7]. Young erythrocytes have also been reported to show increased susceptibility to invasion by the malaria parasites Plasmodium falciparum [23], P. berghei [21] and P. vivax [11,13].Reticulocytes differ from mature erythrocytes in the following ways. Reticulocytes are larger and have a great excess of membrane in relation to their contents. The cytoplasm contains ribosomes, polyribosomes and mitochondria. They have a higher concentration of adenosine triphosphate (ATP), reduced glutathione (GSH), amino acids and nucleic acids than mature erythrocytes [13]. These compounds may be essential for multiplication of the parasites. Furthermore, dynamic changes in the reticulocyte membrane occur during maturation of the reticulocytes into mature erythrocytes, e. g., remodeling of the membrane skeleton and cytoskeleton [2], the formation of exosomes as a mechanism for the selective loss of the membrane transferrin receptor, and surface-area reduction [9][10]. For several malaria species, successful invasion of erythrocytes has been reported to be associated with the presence of receptors to which malarial merozoites attach on the erythrocyte membrane [5,10,21,28]. It is possible that loss of the receptors for B. gibsoni parasites could occur with the aging of erythrocytes. On the other hand, it has been reported that the...

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Section: Discussionsupporting

confidence: 70%

The Cause of the Predilection of Babesia gibsoni for Reticulocytes.

Yamasaki

Otsuka

Yamato

et al. 2000

The Journal of Veterinary Medical Science

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“…Some radioactivity from labeled hemoglobin is incorporated into parasite protein (3). However, P. falciparum grows poorly in medium lacking any one of seven amino acids and is sluggish when grown in medium containing only the five amino acids on which it is most reliant (4,5). These findings suggest a dependence on exogenously supplied amino acids.…”

Section: Degradation Of Host Hemoglobin By the Human Malaria Parasitementioning

confidence: 56%

Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems

Istvan

Gluzman

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

325

333

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Degradation of host hemoglobin by the human malaria parasitePlasmodium falciparum is a massive metabolic process. What role this degradation plays and whether it is essential for parasite survival have not been established, nor have the roles of the various degradative enzymes been clearly defined. We report that P. falciparum can grow in medium containing a single amino acid (isoleucine, the only amino acid missing from human hemoglobin). In this medium, growth of hemoglobin-degrading enzyme gene knockout lines (missing falcipain-2 and plasmepsins alone or in combination) is impaired. Blockade of plasmepsins with the potent inhibitor pepstatin A has a minimal effect on WT parasite growth but kills falcipain-2 knockout parasites at low concentrations and is even more potent on falcipain-2, plasmepsin I and IV triple knockout parasites. We conclude that: (i ) hemoglobin degradation is necessary for parasite survival; (ii ) hemoglobin degradation is sufficient to supply most of the parasite's amino acid requirements; (iii ) external amino acid acquisition and hemoglobin digestion are partially redundant nutrient pathways; (iv) hemoglobin degradation uses dual protease families with overlapping function; and (v) hemoglobin-degrading plasmepsins are not promising drug targets.hemoglobin ͉ malaria ͉ protease

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“…Like virtually all growing and replicating cells, the intraerythrocytic parasite requires purines and pyrimidines for the synthesis of a range of important molecules including those involved in heredity (DNA), protein synthesis (RNA), bioenergetics (ATP, ADP) and cell signalling (cAMP, GTP). The malaria parasite, like other parasitic protozoa characterized to date, has the enzymes required for the de novo synthesis of pyrimidines, but lacks those for the synthesis of purines Landfear et al ., 2004;de Koning et al ., 2005); the growth of the intraerythrocytic malaria parasite is therefore reliant on the parasite salvaging purines from its external environment (Divo et al ., 1985).…”

Section: Introductionmentioning

confidence: 99%

Transport of nucleosides across the Plasmodium falciparum parasite plasma membrane has characteristics of PfENT1

Downie¹,

Saliba

Howitt³

et al. 2006

Molecular Microbiology

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SummaryLike all parasitic protozoa, the human malaria parasite Plasmodium falciparum lacks the enzymes required for de novo synthesis of purines and it is therefore reliant upon the salvage of these compounds from the external environment. P. falciparum equilibrative nucleoside transporter 1 (PfENT1) is a nucleoside transporter that has been localized to the plasma membrane of the intraerythrocytic form of the parasite. In this study we have characterized the transport of purine and pyrimidine nucleosides across the plasma membrane of 'isolated' trophozoite-stage P. falciparum parasites and compared the transport characteristics of the parasite with those of PfENT1 expressed in Xenopus oocytes. The transport of nucleosides into the parasite: (i) was, in the case of adenosine, inosine and thymidine, very fast, equilibrating within a few seconds; (ii) was of low affinity [ K m (adenosine) = 1.45 ± 0.25 mM; K m (thymidine) = 1.11 ± 0.09 mM]; and (iii) showed 'crosscompetition' for adenosine, inosine and thymidine, but not cytidine. The kinetic characteristics of nucleoside transport in intact parasites matched very closely those of PfENT1 expressed in Xenopus oocytes [ K m (adenosine) = 1.86 ± 0.28 mM; K m (thymidine) = 1.33 ± 0.17 mM]. Furthermore, PfENT1 transported adenosine, inosine and thymidine, with a cross-competition profile the same as that seen for isolated parasites. The data are consistent with PfENT1 serving as a major route for the uptake of nucleosides across the parasite plasma membrane.

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Nutritional Requirements of Plasmodium falciparum in Culture. I. Exogenously Supplied Dialyzable Components Necessary for Continuous Growth

Cited by 207 publications

References 45 publications

The Cause of the Predilection of Babesia gibsoni for Reticulocytes.

The Cause of the Predilection of Babesia gibsoni for Reticulocytes.

Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems

Transport of nucleosides across the Plasmodium falciparum parasite plasma membrane has characteristics of PfENT1

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