scholarly journals DNA replication dynamics during erythrocytic schizogony in the malaria parasites Plasmodium falciparum and Plasmodium knowlesi

2021 ◽  
Author(s):  
Jennifer McDonald ◽  
Catherine J Merrick
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Knowlesi ◽  
Malaria Parasites ◽  
Cell Cycles ◽  
New Information ◽  
Extreme Variability ◽  
Single Mass ◽  
Parasite Replication ◽  
First Time ◽  
High Parasite

Malaria parasites are unusual, early-diverging protozoans with non-canonical cell cycles. They do not undergo binary fission, but divide primarily by schizogony. This is a syncytial mode of replication involving asynchronous production of multiple nuclei within the same cytoplasm, culminating in a single mass cytokinesis event. The rate and efficiency of parasite replication is fundamentally important to malarial disease, which tends to be severe in hosts with high parasite loads. Here, we have studied for the first time the dynamics of schizogony in two human malaria parasite species, Plasmodium falciparum and Plasmodium knowlesi. These differ in their cell-cycle length, the number of progeny produced and the genome composition, among other factors. Comparing them could therefore yield new information about the parameters and limitations of schizogony. We report that the dynamics of schizogony differ significantly between these two species, most strikingly in the gap phases between successive nuclear replications, which are longer in P. falciparum and shorter, but more heterogenous, in P. knowlesi. In both species, gaps become longer as schizogony progresses, whereas each period of active replication grows shorter. In both species there is also extreme variability between individual cells, with some schizonts producing many more nuclei than others, and some individual nuclei arresting their replication for many hours while adjacent nuclei continue to replicate. The efficiency of schizogony is probably influenced by a complex set of factors in both the parasite and its host cell.

scholarly journals Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes atp6 (Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca2+ ATPase), tctp, mdr1, and cg10

2006 ◽  
Vol 50 (2) ◽  
pp. 480-489 ◽  
Author(s):  
A. Afonso ◽  
P. Hunt ◽  
S. Cheesman ◽  
A. C. Alves ◽  
C. V. Cunha ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasmodium Falciparum ◽  
Copy Number ◽  
Malaria Parasite ◽  
Field Studies ◽  
Rodent Malaria Parasite ◽  
Malaria Parasites ◽  
Rodent Malaria ◽  
First Time ◽  
Genetic Modulators

ABSTRACT Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.

scholarly journals Transfected Plasmodium knowlesi Produces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites

2003 ◽  
Vol 71 (8) ◽  
pp. 4375-4381 ◽  
Author(s):  
Hastings Ozwara ◽  
Jan A. M. Langermans ◽  
Clemens H. M. Kocken ◽  
Annemarie van der Wel ◽  
Peter H. van der Meide ◽  
...  
Keyword(s):  
Plasmodium Knowlesi ◽  
Gamma Interferon ◽  
Parasite Development ◽  
Malaria Parasites ◽  
Developmentally Regulated ◽  
Apical Membrane Antigen 1 ◽  
Ifn Γ ◽  
New Perspective ◽  
First Time

ABSTRACT Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-γ) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-γ under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-γ in a developmentally regulated manner. IFN-γ expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-γ was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.

scholarly journals Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica R. Loughland ◽  
Tonia Woodberry ◽  
Damian Oyong ◽  
Kim A. Piera ◽  
Fiona H. Amante ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Experimental Infection ◽  
Plasmodium Knowlesi ◽  
Plasmodium Falciparum Malaria ◽  
Flt3 Ligand ◽  
Elevated Plasma ◽  
Zoonotic Parasite ◽  
First Time ◽  
Submicroscopic Infection

Abstract Background Plasmodium falciparum malaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection. Methods Plasma Flt3L concentration and blood CD141+ DC, CD1c+ DC and plasmacytoid DC (pDC) numbers were assessed in (i) volunteers experimentally infected with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria. Results Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria with no increase in a subclinical experimental infection. Circulating CD141+ DCs, CD1c+ DCs and pDCs declined in all adults tested, for the first time extending the finding of DC subset decline in acute malaria to the zoonotic parasite P. knowlesi. Conclusions In adults, submicroscopic Plasmodium infection causes no change in plasma Flt3L but does reduce circulating DCs. Plasma Flt3L concentrations increase in acute malaria, yet this increase is insufficient to restore or expand circulating CD141+ DCs, CD1c+ DCs or pDCs. These data imply that haematopoietic factors, yet to be identified and not Flt3L, involved in the sensing/maintenance of circulating DC are impacted by malaria and a submicroscopic infection. The zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria.

scholarly journals Optimization of CRISPR/Cas System for Improving Genome Editing Efficiency in Plasmodium falciparum

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuemeng Zhao ◽  
Fei Wang ◽  
Changhong Wang ◽  
Xiaobai Zhang ◽  
Cizhong Jiang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genome Editing ◽  
Gene Editing ◽  
Molecular Mechanisms ◽  
Related Gene ◽  
Malaria Parasites ◽  
Human Malaria Parasite ◽  
Genome Feature ◽  
First Time ◽  
Transgenic Strains

Studies of molecular mechanisms and related gene functions have long been restricted by limited genome editing technologies in malaria parasites. Recently, a simple and effective genome editing technology, the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system, has greatly facilitated these studies in many organisms, including malaria parasites. However, due to the special genome feature of malaria parasites, the manipulation and gene editing efficacy of the CRISPR/Cas system in this pathogen need to be improved, particularly in the human malaria parasite, Plasmodium falciparum. Herein, based on the CRISPR/Cas9 system, we developed an integrating strategy to generate a Cas9i system, which significantly shortened the time for generation of transgenic strains in P. falciparum. Moreover, with this Cas9i system, we have successfully achieved multiplexed genome editing (mutating or tagging) by a single-round transfection in P. falciparum. In addition, we for the first time adapted AsCpf1 (Acidaminococcus sp. Cpf1), an alternative to Cas9, into P. falciparum parasites and examined it for gene editing. These optimizations of the CRISPR/Cas system will further facilitate the mechanistic research of malaria parasites and contribute to eliminating malaria in the future.

scholarly journals Adaptation of the [3H]Hypoxanthine Uptake Assay forIn Vitro-Cultured Plasmodium knowlesi Malaria Parasites

2016 ◽  
Vol 60 (7) ◽  
pp. 4361-4363 ◽  
Author(s):  
Megan S. J. Arnold ◽  
Jessica A. Engel ◽  
Ming Jang Chua ◽  
Gillian M. Fisher ◽  
Tina S. Skinner-Adams ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Discovery ◽  
Malaria Parasite ◽  
Plasmodium Knowlesi ◽  
Malaria Parasites ◽  
Content Type ◽  
Zoonotic Malaria ◽  
Uptake Assay

ABSTRACTThe zoonotic malaria parasitePlasmodium knowlesihas recently been established in continuousin vitroculture. Here, thePlasmodium falciparum[3H]hypoxanthine uptake assay was adapted forP. knowlesiand used to determine the sensitivity of this parasite to chloroquine, cycloguanil, and clindamycin. The data demonstrate thatP. knowlesiis sensitive to all drugs, with 50% inhibitory concentrations (IC50s) consistent with those obtained withP. falciparum. This assay provides a platform to useP. knowlesi in vitrofor drug discovery.

A memoir of Hugh Miller (1802–1856) attributed to his son Hugh Miller FGS (1850–1896)

2017 ◽  
Vol 44 (1) ◽  
pp. 103-109 ◽  
Author(s):  
M. A. Taylor
Keyword(s):  
Family Member ◽  
New Information ◽  
Newspaper Editor ◽  
Interesting Contribution ◽  
First Time

A manuscript memoir of Hugh Miller (1802–1856), geologist, writer and newspaper editor, is attributed to his son Hugh Miller FGS (1850–1896). It is published here, apparently for the first time. It was written sometime in 1881–1896, more probably 1882–1895. Its intended place of publication is discussed. It is an interesting contribution to Miller biography, written by a family member and providing some new information and anecdotes.

scholarly journals Non-human primate and human malaria: past, present and future

2021 ◽  
Author(s):  
Spinello Antinori ◽  
Cecilia Bonazzetti ◽  
Andrea Giacomelli ◽  
Mario Corbellino ◽  
Massimo Galli ◽  
...  
Keyword(s):  
Plasmodium Knowlesi ◽  
Plasmodium Species ◽  
Molecular Techniques ◽  
Malaria Parasites ◽  
Human Malaria ◽  
Complex Interactions ◽  
Zoonotic Malaria ◽  
The Impact ◽  
Human Plasmodium ◽  
Human Primate

Abstract Background Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites. This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease. Results The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria. Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria. Conclusions Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies.

scholarly journals Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yifat Ofir-Birin ◽  
Hila Ben Ami Pilo ◽  
Abel Cruz Camacho ◽  
Ariel Rudik ◽  
Anna Rivkin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Cerebral Malaria ◽  
Survival Strategy ◽  
Parasitic Disease ◽  
Malaria Parasites ◽  
Sensing System ◽  
Rich Domain ◽  
Cargo Delivery ◽  
Low Levels

AbstractPathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

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