Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-22T01:21:32.190Z Has data issue: false hasContentIssue false
  • English
  • Français

Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle

Published online by Cambridge University Press:  06 April 2009

R. E. Sinden  and
M. E. Smalley
R. E. Sinden
Affiliation:
Department of Zoology and Applied Entomology, Imperial College, London SW7 2EE
M. E. Smalley
Affiliation:
Medical Research Council Laboratories, Fajara, P.O. Box 273, Banjul, The Gambia, West Africa
Get access Rights & Permissions [Opens in a new window]

Summary

Reproducible growth of gametocytes of Plasmodium falciparum in vitro was obtained from ring-stages taken directly from naturally infected patients and from the same material following storage in liquid nitrogen. Progressive sexual differentiation in vitro was examined for a finite period of 9 days in microcultures and was, for convenience, divided into 5 stages using established morphological criteria (Hawking, Wilson & Gammage, 1971). This microculture system was adapted as a bioassay for various anti-metabolites. Drug activity was measured by observing the inhibition of the established pattern of sequential development in experimental as compared to control cultures. Inhibitors used were directed against DNA, RNA and protein metabolism and microtubule assembly. As a result of these studies it is proposed that the sexual cell-cycle of P. falciparum is characterized by 4 phases. (1) A G1 period which lasts only a few hours. (2) The S phase, where DNA synthesis occurs, occupies the remainder of the first 2 days of development – both G1 and S are confined to stage I and II gametocytes. (3) G2, which is subdivided into 2 sections: G2A, characterized by stage II and III gametocytes, in which significant RNA and protein synthesis continue to occur; and G2B, where there is a progressive increase in transcription control resulting in the depression of both RNA and protein synthesis. Nonetheless, continued morphological differentiation occurs in the latter section transforming the parasites to stage IV and the morphologically and functionally mature stage V. The final M phase is marked by the brief and explosive events of gametogenesis, during which further protein synthesis occurs de novo. The proposed cell-cycle is examined as a model for studies on the activity of gametocytocidal compounds.

Type
Research Article
Information
Parasitology , Volume 79 , Issue 2 , October 1979 , pp. 277 - 296
Copyright
Copyright © Cambridge University Press 1979

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alger, N. E., Spira, D. T. & Silverman, D. H. (1970). Inhibition of rodent malaria by rifampicin. Nature, London 227, 381–2.CrossRefGoogle ScholarPubMed
Canning, E. U. & Sinden, B. E. (1975). Nuclear organisation in gametocytes of Plasmodium and Hepatocystis: a cytochemical study. Zeitschrift für Parasitenkunde 46, 297–9.CrossRefGoogle ScholarPubMed
Carter, R. & Beace, R. F. (1978). Gametogenesis in culture by gametocytes of Plasmodium falciparum. Nature, London 270, 240–1.CrossRefGoogle Scholar
Field, J. W. & Shute, P. G. (1956). The microscopic diagnosis of human malaria. II. A morphological study of the erythrocytic parasites. Studies from the Institute for Medical Research, Malaya. No. 24, Part II.Google Scholar
Gale, E. F., Cundliffe, E., Reynolds, P. E., Richmond, M. H. & Waring, M. J. (1972). The Molecular Basis of Antibiotic Action. London: John Wiley.Google Scholar
Garnham, P. C. C. (1966). Malaria Parasites and other Haemosporidia. Oxford: Blackwell Scientific Publications.Google Scholar
Gutteridge, W. (1974). Periodicity of DNA synthesis in malaria. In Basic Research on Malaria (ed. Bateman, J. B.), pp. 189–195. E.R.O. Technical Report REO-5–74 European Research Office, U.S. Army R and D group (Europe).Google Scholar
Gutteridge, W. & Coombs, G. (1977). Biochemistry of Parasitic Protozoa. London: Macmillan Press Ltd.CrossRefGoogle Scholar
Gutteridge, W. E. & Trigg, P. I. (1970). Incorporation of radioactive precursors into DNA and RNA of Plasmodium knowlesi in vitro. Journal of Protozoology 17, 89–96.CrossRefGoogle ScholarPubMed
Hawking, F., Wilson, M. E. & Gammage, K. (1971). Evidence for cyclic development and shortlived maturity in the gametocytes of Plasmodium falciparum. Transactions of The Royal Society of Tropical Medicine and Hygiene 65, 549–59.CrossRefGoogle ScholarPubMed
Howell, S. H., Blaschko, W. J. & Drew, C. H. (1975). Inhibitor effects during the cell cycle of Chlamydamonas reinhardtii. Determination of transition points in asynchronous cultures. Journal of Cell Biology 67, 126–35.CrossRefGoogle Scholar
Irvin, A. D. & Young, E. R. (1977). Possible in vitro test for screening drugs for activity against Babesia and other blood protozoa. Nature, London 269, 407–9.CrossRefGoogle ScholarPubMed
Jeffery, G. M. & Eyles, D. E. (1955). Infectivity to mosquitoes of Plasmodium falciparum as related to gametocyte density and duration of infection. American Journal of Tropical Medicine and Hygiene 4, 781–9.CrossRefGoogle ScholarPubMed
Jeffery, G. M., Young, M. D. & Eyles, D. E. (1956). The treatment of Plasmodium falciparum infection with chloroquine, with a note on infectivity to mosquitoes of primaquine-and pyrimethamine-treated cases. American Journal of Hygiene 64, 1–11.Google ScholarPubMed
Jensen, J. B. (1979). Observations on gametocytogenesis in Plasmodium falciparum from continuous culture. Journal of Protozoology 26 (in the Press).CrossRefGoogle Scholar
Jenson, J. B. & Trager, W. (1978). Plasmodium falciparum in culture: establishment of additional strains. American Journal of Tropical Medicine and Hygiene 27, 743–6.CrossRefGoogle Scholar
Omar, M. S., Collins, W. E. & Contacos, P. G. (1974). Gametocytocidal sporontocidal effects of antimalarial drugs on malaria parasites. II. Action of folio reductase inhibitors, chloroguanide, and pyrimethamine against Plasmodium cynomolgi. Experimental Parasitology 36, 167–77.CrossRefGoogle Scholar
Peters, W. (1970). Chemotherapy and Drug Resistance in Malaria. London: Academic Press.Google Scholar
Philips, R. S., Wilson, R. J. M. & Pasvol, G. (1976). Differentiation of gametocytes of Plasmodium falciparum in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 286.Google Scholar
Philips, R. S., Wilson, R. J. M. & Pasvol, G. (1978). Differentiation of gametocytes in microcultures of human blood infected with Plasmodium falciparum. Journal of Protozoology 25, 394–8.CrossRefGoogle Scholar
Sinden, R. E. (1978). Cell biology. In Rodent Malaria (ed. Killick-Kendrick, R. and Peters, W.), pp. 85–168. London: Academic Press.Google Scholar
Sinden, R. E., Canning, E. U., Bray, R. S. & Smalley, M. E. (1978). Gametocyte and gamete development in Plasmodium falciparum. Proceedings of the Royal Society, London, B 201, 375–99.Google ScholarPubMed
Smalley, M. E. (1976). Plasmodium falciparum gametocytogenesis in vitro. Nature, London 264, 271–2.CrossRefGoogle ScholarPubMed
Smalley, M. E. (1977). Plasmodium falciparum gametocytes: the effect of chloroquine on their development. Transactions of the Royal Society of Tropical Medicine and Hygiene 71, 526–9.CrossRefGoogle ScholarPubMed
Smalley, M. E. & Sinden, R. E. (1977). Plasmodium falciparum gametocytes: their longevity and infectivity. Parasitology 74, 1–8.CrossRefGoogle ScholarPubMed
Toyé, P. J., Sinden, R. E. & Canning, E. U. (1977). The action of metabolic inhibitors on microgametogenesis in Plasmodium yoelii nigeriensis. Zeitschrift für Parasitenkunde 53, 133–41.CrossRefGoogle ScholarPubMed
Trager, W. & Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–5.CrossRefGoogle ScholarPubMed
Trigg, P. (1978). Plasmodidae. In Methods of Cultivating Parasites in vitro (ed. Taylor, A. E. R. and Baker, J. B.), pp. 89–110. London: Academic Press.Google Scholar
Warhurst, D. C. (1974). The use of antibiotics and inhibitors upon chloroquine induced autophagic vacuole formation in P. berghei in vitro. In Basic Research on Malaria (ed. Bateman, J. B.), pp. 228–38. E.R.O. Technical Report ERO-5–74 European Research Office, U.S. Army R and D Group (Europe).Google Scholar
Warhurst, D. C., Homewood, C. A., Peters, W. & Baggeley, V. C. (1972). Pigment changes in Plasmodium berghei as indicators of activity and mode of action of antimalarial drugs. Proceedings of the Helminthology Society of Washington 39, 271–8.Google Scholar
Wilkinson, R. N., Colwell, W. J. & Neoy Patimanond, S. (1972). Effect of suphamethoxazole-trimethoprim on the viability of Plasmodium falciparum gametocytes. Transactions of the Royal Society of Tropical Medicine and Hygiene 66, 148–9.Google Scholar