DNA synthesis in Plasmodium berghei during asexual and sexual development

Janse, Chris J.; Klooster, P. F. J. Van Der; Káay, H. J. Van Der; Ploeg, M. van der; Overdulve, J. P.

doi:10.1016/0166-6851(86)90029-0

Cited by 104 publications

(95 citation statements)

References 38 publications

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“…The activated microgametocyte replicates its genome three times, progressing from haploid to octaploid (Janse et al ., 1986, 1988) and mitotically produces eight flagellar microgametes in a process termed exflagellation (Fig. 2).…”

Section: The Formation Of Gametesmentioning

confidence: 99%

“…berghei resulted in male sterility and blocked fertilization (Hirai et al ., 2008; Liu et al ., 2008). Following gamete fusion, nuclear fusion ensues, and over the next 3 h, meiosis occurs, and the zygote becomes tetraploid (Janse et al ., 1986), a process involving the NIMA‐related kinases Nek‐2 and Nek‐4 (Reininger et al ., 2005, 2009). Parasite tetraploidy persists throughout the ookinete stage until sporozoite budding in the oocyst restores the haploid state (Janse et al ., 1986) (Table 1).…”

Section: The Formation Of Gametesmentioning

confidence: 99%

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The development of malaria parasites in the mosquito midgut

Bennink

Kiesow

Pradel

2016

Cellular Microbiology

163

155

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SummaryThe mosquito midgut stages of malaria parasites are crucial for establishing an infection in the insect vector and to thus ensure further spread of the pathogen. Parasite development in the midgut starts with the activation of the intraerythrocytic gametocytes immediately after take‐up and ends with traversal of the midgut epithelium by the invasive ookinetes less than 24 h later. During this time period, the plasmodia undergo two processes of stage conversion, from gametocytes to gametes and from zygotes to ookinetes, both accompanied by dramatic morphological changes. Further, gamete formation requires parasite egress from the enveloping erythrocytes, rendering them vulnerable to the aggressive factors of the insect gut, like components of the human blood meal. The mosquito midgut stages of malaria parasites are unprecedented objects to study a variety of cell biological aspects, including signal perception, cell conversion, parasite/host co‐adaptation and immune evasion. This review highlights recent insights into the molecules involved in gametocyte activation and gamete formation as well as in zygote‐to‐ookinete conversion and ookinete midgut exit; it further discusses factors that can harm the extracellular midgut stages as well as the measures of the parasites to protect themselves from any damage.

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Section: The Formation Of Gametesmentioning

confidence: 99%

Section: The Formation Of Gametesmentioning

confidence: 99%

The development of malaria parasites in the mosquito midgut

Bennink

Kiesow

Pradel

2016

Cellular Microbiology

163

155

View full text Add to dashboard Cite

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“…The finding that the majority of zygotes and ookinetes had more than or equal to four times as much DNA as region R3 is consistent with our current understanding that meiotic division occurs shortly after gamete fusion. 36,37,42,43 It is possible that further refinements of flow cytometric sorting (for example, incorporation of forward-and side-scatter parameters to separate round forms from elongated forms based on size or clumping) might be able to separate zygotes from ookinetes.…”

Section: High-yield Ookinete Productionmentioning

confidence: 99%

“…35,36 This difference in ploidy was exploited to separate P. falciparum zygotes and ookinetes from other sexual stage forms using flow cytometric sorting. Parasites from the 11-16% Nycodenz gradient interface were washed and stained with Vybrant DyeCycle Green stain according to manufacturer's instructions (Molecular Probes; Invitrogen, Carlsbad, CA).…”

Section: High-yield Ookinete Productionmentioning

confidence: 99%

In Vitro Generation of Plasmodium falciparum Ookinetes

Bounkeua¹,

Li²,

Vinetz³

2010

The American Society of Tropical Medicine and Hygiene

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Plasmodium transmission from the human host to the mosquito depends on the ability of gametocytes to differentiate into ookinetes, the invasive form of the parasite that invades and establishes infection in the mosquito midgut. The biology of P. falciparum ookinetes is poorly understood, because sufficient quantities of this stage of this parasite species have not been obtained for detailed study. This report details methods to optimize production of P. falciparum sexual stage parasites, including ookinetes. Flow cytometric sorting was used to separate diploid/tetraploid zygotes and ookinetes from haploid gametetocytes and unfertilized gametes based on DNA content. Consistent production of 106–107 P. falciparum ookinetes per 10 mL culture was observed, with ookinete transformation present in 10–40% of all parasite forms. Transmission electron micrographs of cultured parasites confirmed ookinete development.

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“…Perhaps disagreement in the literature regarding stage specific CQ toxicity is due in part to measurement of survival at different endpoints (wherein different degrees of delayed death have occurred). In any case, collectively, these studies typically only report data for one parasite strain, do not quantify precise IC 50 values for various dose schedules (i.e. continuous vs. bolus pulse for various time), and were performed well before our current level of molecular understanding of CQR and so do not compare CQS vs. CQR parasites.…”

Section: Introductionmentioning

confidence: 99%

Stage independent chloroquine resistance and chloroquine toxicity revealed via spinning disk confocal microscopy

Gligorijevic

Purdy

Elliott

et al. 2008

Molecular and Biochemical Parasitology

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We previously customized a Nipkow spinning disk confocal microscope (SDCM) to acquire 4D data for live, intraerythrocytic malarial parasites (Gligorijevic, B. et al., Biochemistry 45, 12400). We reported that chloroquine (CQ) treatment did not appear to affect progress through the cell cycle, and suggested that toxicity may be manifested post-schizogony. We now use SDCM, synchronized cell culture and continuous vs. bolus drug dosing to investigate stage specific CQ effects in detail. We develop a novel, extremely rapid method for counting schizont nuclei in 3D. We then quantify schizont nuclei and hemozoin (Hz) production for live parasite cultures pulsed with CQ at different stages in the cell cycle and find that bolus treatment of rings affects the multiplicity of nuclear division. We quantify parasitemia and merozoite development in subsequent cycles following bolus CQ exposure and find that a portion of CQ toxicity is manifested post schizogony as "delayed death". Using these methods and others we compare CQ sensitive (CQS) vs. resistant (CQR) strains as well as transfectants that are CQR via introduction of mutant PfCRT. Surprisingly, we find that PfCRT confers resistance to CQ administered at the very early ring stage of development, wherein a digestive vacuole is not yet formed, as well as at the schizont stage, wherein Hz production is thought to plateau. Taken together, these data force a rethinking of CQ pharmacology and the mechanism of CQR.

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DNA synthesis in Plasmodium berghei during asexual and sexual development

Cited by 104 publications

References 38 publications

The development of malaria parasites in the mosquito midgut

The development of malaria parasites in the mosquito midgut

In Vitro Generation of Plasmodium falciparum Ookinetes

Stage independent chloroquine resistance and chloroquine toxicity revealed via spinning disk confocal microscopy

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