Intracellular phagotrophy by malaria parasites: an electron microscope study of Plasmodium lophurae*

Rudzinska, Maria A.; Trager, William

doi:10.1111/j.1550-7408.1957.tb02507.x

Cited by 115 publications

(43 citation statements)

References 29 publications

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“…This suggests a disruption of parasite metabolism in the sickled cell. One possibility is an inhibition of the endocytic feeding process of the plasmodium (19), though a less obvious mechanism may be acting.…”

Section: Methodsmentioning

confidence: 99%

Erythrocytic mechanism of sickle cell resistance to malaria.

Friedman¹

1978

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

260

151

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The physiological basis for the resistance to falciparum malaria o individuals with sickle cell trait has not been understood. Recent advances in erythrocytic Plasmodium falciparum culture have made possible a direct investigation of the development of the malaria parasite in cells with sickle cell hemoglobin. In a high (18%) oxygen atmosphere, there is no apparent sickling of cells, and the growth and multiplication of P. falciparum is identical in normal (AA), hemoglobin S homozygous (SS), and hemoglobin S heterozygous (SA) erythrocytes. Cultures under low (1-5%) oxygen, however, showed clear inhibition of growth. The sickling of SS red cells killed and lysed most or all of the intracellular parasites. Parasites in SA red cells were killed primarily at the large ring stage, probably as a result of a disruption of the parasite metabolism. Incubation in cyanate prior to culture reversed the resistance of SA erythrocytes to plasmodium growth, but had no effect on SS red cell sickling or resistance. Thus, the mechanism of resistance in vivo may be due solely to intraerythrocytic conditions. In 1949, the elucidation of the genetic basis for sickle cell anemia (SS) and sickle cell trait (SA) (1, 2) and the demonstration of the involvement of an abnormal hemoglobin in the disease (3) formed a link between genes and molecules. At the same time, medical scientists working in Africa suggested that sickle cell gene carriers were resistant to falciparum malaria (4, 5), thereby forging a connection between molecules and selective pressure. It was proposed that the inheritance of this variant hemoglobin gene conferred resistance in the heterozygous state to falciparum malaria, which is often lethal in the early years of life. The greater ability of heterozygotes to survive to the age of reproduction was thought to balance the almost complete mortality of the homozygous state. In the entire chain between genes and evolution, the weakest link has been that describing the intimate relationship between sickle cell hemoglobin (Hb S) and the malaria parasite, Plasmodium falciparum. Population studies have confirmed that children heterozygous for Hb S are protected, statistically, from death, though not infection, by P. falciparum (6). Thus far, however, a direct connection between sickling and resistance has remained suggestive and speculative.The erythrocytic cycle of the parasite proceeds from an infective form, the merozoite. Infection occurs by induced endocytosis, and the growth of the early ring to a trophozoite follows. Nuclear division precedes segmentation of the mature schizont into 16 or more merozoites, which are released upon lysis of the red blood cell. The entire cycle requires 48 hr, the latter two-thirds with the parasitized cell sequestered in the vascular network of the tissues. The periodic fever of malaria results from the synchronous lysis of infected cells upon maturation of the parasite.In the Hb S-containing red cell, the parasite may not find as perfect a host as the one to which it is adapted. ...

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Section: Methodsmentioning

confidence: 99%

Erythrocytic mechanism of sickle cell resistance to malaria.

Friedman¹

1978

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

260

151

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“…The mechanism of feeding in malarial parasites has been the subject of a number of papers, most notably those from the laboratory of Rudzinska and Trager (17)(18)(19)(20). Their studies on the fine structure of actively growing erythrocytic stages of Plasmodium lophurae and P. berghei demonstrated the presence of food vacuoles which they believed to be formed by random invagination of the parasite membrane around red cell cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

The Feeding Mechanism of Avian Malarial Parasites

Aikawa

Hepler

Huff

et al. 1966

The Journal of Cell Biology

169

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Electron microscope studies of the erythrocytic forms, including gametocytcs and asexual schizonts, of the protozoa Plasmodium fallax, P. lophurae, and P. cathemerium, have revealed a "cytostome," a specialized organclle of thc pcllicular membrane which is activc in the ingestion of host cell cytoplasm. In matcrial fixed in glutaraldehyde and postfixed in OsO~, thc cytostomc appears in face view as a pore limited by two dense circular membrancs and having an inside diameter of approximately 190 m/~. In cross-section, the cytostome is a cavity boundcd on each side by two dcnse scgments corresponding to the two dcnsc circles observed in facc view; its basc consists of a single unit mcmbranc. In the process of feeding, the cytostome cavity cnlarges by expansion of its membranc, permitting a large quantity of red ccll cytoplasm to come into contact with the cytostome wall. Subsequcnt digcstion of erythrocyte cytoplasm occurs exclusively in food vacuoles which emanatc from the cytostomc invagination. As digcstion progrcsscs, the food vacuoles initially stain more densely and thcrc is a marked build-up of hcmozoin granules. In the final stagc of digcstion, a single membrane surrounds a cluster of residual pigment particles and very little of the original host cell cytoplasm remains. The cytostome in exoerythrocytic stages of P. fallax has been observed only in merozoites and does not seem to play the same role in the feeding mechanism.

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“…Accordingly, it is highly significant that the specific activities (in relation to hemoglobin content) of all the enzymes of CoA biosynthesis were the same in infected as in uninfected duck erythrocytes. When large parasites were present (in 5-day infections) that had ingested and digested appreciable amounts of host cell cytoplasm (15) (14).…”

mentioning

confidence: 99%

Coenzyme A requirement of malaria parasites: enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae.

Brohn¹,

Trager²

1975

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

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Normal Cell Isolation. Detailed procedures for maintaining heavy synchronous infections of these parasites and for isolating erythrocytes or host-free parasites have been described (6, 7). Giemsa-stained thin blood films were used to determine the extent of parasitemia (expressed as the total number of parasites per 100 erythrocytes) and the development stage of the parasite population. The erythrocytes and cell-free parasites used in these studies were obtained from control ducks, ducks infected with small parasites at the uninucleate trophozoite stage of development (4th day after passage), and ducks infected with larger parasites at the multinucleate schizont stage of infection (5th day after passage). Only blood with heavy infections (90-130%) and with 80-90% of either uninucleate or multinucleate parasites was used.Enzyme Preparation. All operations were carried out at 4°. Washed, packed erythrocytes from control and infected ducks or host-free parasites were susl)ended in four times their packed cell volume of 0.05 M Tris HCl buffer, pH 7.5, and passed through a French pressure cell at 8000 lbs./inch2 (562.4 kg/cm2). Wet-mount slides of homogenized cells were observed with a microscope to estimate the degree of cell breakage. The homogenized cell suspensions were centrifuged at 13,000 X g for 0.5 hr in a Sorvall RC2-B refrigerated centrifuge, and the supernatants from this step were assayed directly for enzyme activity.Assays. Phosphopantothenoylcysteine synthetase (pantothenate 4'-phosphate: L-cysteine ligase; EC 6.3.2.5), phospho-

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Intracellular phagotrophy by malaria parasites: an electron microscope study of Plasmodium lophurae*

Cited by 115 publications

References 29 publications

Erythrocytic mechanism of sickle cell resistance to malaria.

Erythrocytic mechanism of sickle cell resistance to malaria.

The Feeding Mechanism of Avian Malarial Parasites

Coenzyme A requirement of malaria parasites: enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae.

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