scholarly journals Estimation of inbreeding coefficients from genotypic data on multiple alleles, and application to estimation of clonality in malaria parasites

1995 ◽  
Vol 65 (1) ◽  
pp. 53-61 ◽  
Author(s):  
William G. Hill ◽  
Hamza A. Babiker ◽  
Lisa C. Ranford-Cartwright ◽  
David Walliker
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Effective Number ◽  
Identity By Descent ◽  
Malaria Parasites ◽  
Multiple Alleles ◽  
Human Host ◽  
Inbreeding Coefficients ◽  
Genotype Frequencies

SummaryMethods for estimating probability of identity by descent (f) are derived for data on numbers of genotypes at single loci and at pairs of loci with many alleles at each locus. The methods are general, but are specifically applied to data on genotype frequencies in zygotes of the malaria parasite sampled from its mosquito host in order to find the extent of outcrossing in the parasite and the degree of clonality in populations. It is assumed that zygotes are the outcome either of gametes of the same clone, in which they are identical at all loci, or are products of two random, unrelated clones. From the estimate of f an effective number of clones per human host can also be derived. For Plasmodium falciparum from a Tanzanian village, estimates of f are 0·33 from data on zygote frequencies at two multiallelic loci, indicating that two-thirds of zygotes produce recombinant types.

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 Quantifying connectivity between local Plasmodium falciparum malaria parasite populations using identity by descent

PLoS Genetics ◽  
2017 ◽  
Vol 13 (10) ◽  
pp. e1007065 ◽  
Author(s):  
Aimee R. Taylor ◽  
Stephen F. Schaffner ◽  
Gustavo C. Cerqueira ◽  
Standwell C. Nkhoma ◽  
Timothy J. C. Anderson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria ◽  
Identity By Descent ◽  
Parasite Populations

scholarly journals The P Domain of the P0 Protein of Plasmodium falciparum Protects against Challenge with Malaria Parasites

2004 ◽  
Vol 72 (9) ◽  
pp. 5515-5521 ◽  
Author(s):  
K. Rajeshwari ◽  
Kalpesh Patel ◽  
Savithri Nambeesan ◽  
Monika Mehta ◽  
Alfica Sehgal ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Monoclonal Antibodies ◽  
Malaria Parasite ◽  
Malaria Parasites ◽  
P0 Protein ◽  
P Domain ◽  
The Absolute ◽  
Domain Peptide ◽  
Parasite Challenge

ABSTRACT Monoclonal antibodies (MAbs) specific for the P domain of the Plasmodium falciparum P0 phosphoriboprotein (PfP0) blocked the invasion of RBCs by P. falciparum. Vaccination with this P-domain peptide protected mice upon malaria parasite challenge. The absolute specificity of the MAbs and the PfP0 P peptide makes them potential protective malaria reagents.

scholarly journals The Clp System in Malaria Parasites Degrades Essential Substrates to Regulate Plastid Biogenesis

2019 ◽  
Author(s):  
A. Florentin ◽  
D.R. Stephens ◽  
C.F. Brooks ◽  
R.P. Baptista ◽  
V Muralidharan
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Affinity Purification ◽  
Nuclear Genome ◽  
Clp Protease ◽  
Complex Composition ◽  
Malaria Parasites ◽  
Human Malaria Parasite ◽  
Essential Function ◽  
Comprehensive Study

AbstractThe human malaria parasite, Plasmodium falciparum, contains an essential plastid called the apicoplast. Most of apicoplast proteins are encoded by the nuclear genome and it is unclear how the plastid proteome is regulated. Here, we study an apicoplast-localized caseinolytic-protease (Clp) system and how it regulates organelle proteostasis. Using null and conditional mutants, we demonstrated that the Clp protease (PfClpP) has robust enzymatic activity that is essential for apicoplast biogenesis. We developed a CRISPR/Cas9 based system to express catalytically-dead PfClpP, which showed that PfClpP oligomerizes as a zymogen and matured via trans-autocatalysis. The expression of a Clp chaperone (PfClpC) mutant led to the discovery of a functional chaperone-protease interaction essential for plastid function. Conditional mutants of the substrate-adaptor (PfClpS) demonstrated its essential function in plastid biogenesis. A combination of multiple affinity purification screens identified the Clp complex composition as well as putative Clp substrates. This comprehensive study reveals the molecular composition and interactions influencing the proteolytic function of the apicoplast Clp system and demonstrates its central role in the biogenesis of the plastid in malaria parasites.

scholarly journals A new malaria parasite of man

1914 ◽  
Vol 87 (596) ◽  
pp. 375-377 ◽  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Red Cells ◽  
Field Of View ◽  
Malaria Parasites ◽  
Blood Slide ◽  
Native Child

In the autumn of 1913 Major Kenrick, I. M. S., kindly sent me, from Pachmari, Central Provinces, India, a blood slide from a native child, containing numerous malaria parasites. On examining these, which I at first took to be malignant tertian parasites, the suspicion arose in my mind that there was something peculiar about their appearance. I happened just previously to have been studying a blood slide from Rhodesia, containing very numerous malignant tertian parasites. The peculiarity of the Indian parasite, as far as I could at first define it, was that it was an irregular parasite as compared with the regular, almost monotonous, contour of the “rings” of the malignant tertian parasite ( Plasmodium falciparum ). I proceeded then to study the Indian parasite more carefully; and, after-daily observations for many weeks of it, and of control malignant tertian parasites from various sources, I came definitely to the conclusion that it was unlike any malignant tertian parasite that I had ever seen or that I could find figured in the text-books or journals. I also considered carefully the possibility of its being the simple tertian parasite, but to this point I shall return later. During this study, in order to fix my impressions, I drew 150 consecutive parasites from the Indian slide and the Rhodesian slide respectively, as the former appeared in the field of view of an ocular so restricted by placing a diaphragm in it that only half a dozen red cells were visible in the field at a time, thus effectively preventing any selection on my part. I reproduce as pen-and-ink drawings 35 of each series taken at random, as they show very well in a general way the different aspect of the two parasites. For the same purpose I also drew a number of young simple tertian parasites. I now proceed to define as far as possible in detail the peculiarities of this parasite.

scholarly journals Expansion microsopy reveals Plasmodium falciparum blood-stage parasites undergo anaphase with a chromatin bridge in the absence of mini-chromosome maintenance complex binding protein

2021 ◽  
Author(s):  
Benjamin Liffner ◽  
Sabrina Absalon
Keyword(s):  
Plasmodium Falciparum ◽  
Nuclear Envelope ◽  
Malaria Parasite ◽  
Binding Protein ◽  
Nuclear Morphology ◽  
Mitotic Spindles ◽  
Human Host ◽  
The Individual ◽  
Chromatin Bridges

ABSTRACTMitosis in the malaria parasite Plasmodium falciparum undergoes closed mitosis, which occurs within an intact nuclear envelope, and differs significantly from its human host. Mitosis is underpinned by the dynamics of microtubules and the nuclear envelope. To date, our ability to study P. falciparum mitosis by microscopy has been hindered by the small size of P. falciparum nuclei. Ultrastructure expansion microscopy (U-ExM) has recently been developed for P. falciparum, allowing visualization of mitosis at the individual nucleus level. Using U-ExM, three intranuclear microtubule structures are observed: hemispindles, mitotic spindles and interpolar spindles. A previous study demonstrated that the mini-chromosome maintenance complex binding-protein (MCMBP) depletion caused abnormal nuclear morphology and microtubule defects. To investigate the role of microtubules following MCMBP depletion and study the nuclear envelope in these parasites, we developed the first nuclear stain enabled by U-ExM in P. falciparum. MCMBP deficient parasites show aberrant hemispindles and mitotic spindles. Moreover, anaphase chromatin bridges, and individual nuclei containing multiple microtubule structures were observed following MCMBP knockdown. Collectively, this study refines our model for the phenotype of MCMBP-deficient parasites and highlights the utility of U-ExM coupled with a nuclear envelope stain for studying mitosis in P. falciparum.

scholarly journals Characterization of Apicomplexan Amino Acid Transporters (ApiATs) in the Malaria Parasite Plasmodium falciparum

mSphere ◽  
2021 ◽  
Author(s):  
Jan Stephan Wichers ◽  
Carolina van Gelder ◽  
Gwendolin Fuchs ◽  
Julia Mareike Ruge ◽  
Emma Pietsch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Malaria Parasite ◽  
Host Cells ◽  
Amino Acid Transporters ◽  
Malaria Parasites ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Intracellular Proliferation

Malaria parasites live and multiply inside cells. To facilitate their extremely fast intracellular proliferation, they hijack and transform their host cells.

scholarly journals Heat shock modulates the expression of sirtuins and var genes in the malaria parasite Plasmodium falciparum

2020 ◽  
Author(s):  
Linda Anagu ◽  
David Hulse ◽  
Srabasti Chakravorty ◽  
Paul Horrocks ◽  
Catherine Jill Merrick
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Heat Stress ◽  
Heat Shock ◽  
Malaria Parasite ◽  
Severe Disease ◽  
Expression Patterns ◽  
Stress Factors ◽  
High Expression ◽  
Human Host

Abstract Background: In the malaria parasite Plasmodium falciparum the expression of key ‘var’ virulence genes is regulated through epigenetic mechanisms. Two deacetylase enzymes of the sirtuin family have been implicated in this epigenetic control in laboratory-adapted parasites. A previous study of var gene expression in parasites isolated directly from Gambian malaria patients found that high expression levels of severe-disease-associated var variants correlated with high expression of the PfSir2A sirtuin, and these expression patterns also correlated with patient phenotypes of fever and hyperlactataemia. Together, the observations suggest a mechanism through which stress phenotypes in the human host might be sensed via a parasite sirtuin, and virulence gene expression modulated accordingly. Methods: In vitro experiments were conducted using recently-laboratory-adapted Kenyan isolates of P. falciparum to follow up the correlative findings of the field study. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, RT-PCR was used to measure the expression of sirtuins and var genes after cultured parasites had been exposed to 2h or 6h of heat shock at 40°C or elevated lactate at 5mM.Results: Heat shock was shown to influence the expression of both sirtuins and var genes, whereas exposure to lactate was not. Heat shock in the trophozoite stage resulted in modest upregulation of the expression of sirtuins, particularly PfSir2B, by 2-3 fold in all strains tested. Interestingly, when heat shock was applied in ring stages PfSir2A was still upregulated but PfSir2B was downregulated. This correlated with a general upregulation of ring-stage var transcription, and particularly of severe-disease-associated upsA and upsB var genes, but there was no clear pattern in the dominant var gene(s) ultimately expressed by heat-shocked parasites. Conclusions: This study demonstrates for the first time that heat stress in recently-laboratory-adapted patient isolates of P. falciparum results in altered sirtuin expression – PfSir2B as well as PfSir2A – and also the upregulation of var gene expression. These may be strategies evolved by the parasite to survive heat stress when a human host experiences malarial fevers. By contrast, the association between hyperlactataemia and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative.

scholarly journals Phosphorylation of protein 4.1 in Plasmodium falciparum-infected human red blood cells

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3339-3345 ◽  
Author(s):  
AH Chishti ◽  
GJ Maalouf ◽  
S Marfatia ◽  
J Palek ◽  
W Wang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasma Membrane ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Malaria Parasites ◽  
Protein 4.1 ◽  
Human Red Blood Cells ◽  
Human Rbcs

The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont stage malaria parasites. However, the identity of this 80-kD phosphoprotein is controversial. One line of evidence suggests that this protein is a phosphorylated form of RBC protein 4.1 and that it forms a tight complex with the mature parasite-infected erythrocyte surface antigen. In contrast, evidence from another group indicates that the 80-kD protein is derived from the intracellular malaria parasite. To resolve whether the 80-kD protein is indeed RBC protein 4.1, we made use of RBCs obtained from a patient with homozygous 4.1(-) negative hereditary elliptocytosis. RBCs from this patient are completely devoid of protein 4.1. We report here that this lack of protein 4.1 is correlated with the absence of phosphorylation of the 80-kD protein in parasite- infected RBCs, a finding that provides conclusive evidence that the 80- kD phosphoprotein is indeed protein 4.1. In addition, we also identify and partially characterize a casein kinase that phosphorylates protein 4.1 in P falciparum-infected human RBCs. Based on these results, we suggest that the maturation of malaria parasites in human RBCs is accompanied by the phosphorylation of protein 4.1. This phosphorylation of RBC protein 4.1 may provide a mechanism by which the intracellular malaria parasite alters the mechanical properties of the host plasma membrane and modulates parasite growth and survival in vivo.

scholarly journals Heat Shock Modulates The Expression of Sirtuins and Var Genes in The Malaria Parasite Plasmodium Falciparum

2020 ◽  
Author(s):  
Linda O. Anagu ◽  
David R. Hulse ◽  
Srabasti J Chakravorty ◽  
Paul D. Horrocks ◽  
Catherine Jill Merrick
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Heat Stress ◽  
Heat Shock ◽  
Malaria Parasite ◽  
Severe Disease ◽  
Expression Patterns ◽  
Stress Factors ◽  
High Expression ◽  
Human Host

Abstract Background: In the malaria parasite Plasmodium falciparum the expression of ‘var’ virulence genes is regulated through epigenetic mechanisms. Two deacetylase enzymes of the sirtuin family have been implicated in this epigenetic control in laboratory-adapted parasites. A previous study of var gene expression in parasites isolated directly from Gambian malaria patients found that high expression levels of severe-disease-associated var variants correlated with high expression of the PfSir2A sirtuin, and these expression patterns also correlated with patient phenotypes of fever and hyperlactataemia. Together, the observations suggest a mechanism through which stress phenotypes in the human host might be sensed via a parasite sirtuin, and virulence gene expression modulated accordingly. Methods: In vitro experiments were conducted using recently-laboratory-adapted Kenyan isolates of P. falciparum to follow up the correlative findings of the field study. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after cultured parasites had been exposed to 2h or 6h of heat shock at 40°C or elevated lactate at 5mM.Results: Heat shock was shown to influence the expression of both sirtuins and var genes, whereas exposure to lactate was not. Heat shock in the trophozoite stage resulted in modest upregulation of the expression of sirtuins, particularly PfSir2B, by 2-3 fold in all strains tested. Interestingly, when heat shock was applied in ring stages PfSir2A was still upregulated but PfSir2B was downregulated. This correlated with a general upregulation of ring-stage var transcription, and particularly of severe-disease-associated upsA and upsB var genes, but there was no clear pattern in the dominant var gene(s) ultimately expressed by heat-shocked parasites. Conclusions: This study demonstrates for the first time that heat stress in recently-laboratory-adapted isolates of P. falciparum results in altered sirtuin expression – PfSir2B as well as PfSir2A – and also the upregulation of var gene expression. These may be strategies evolved by the parasite to survive heat stress when a human host experiences malarial fevers. By contrast, the association between hyperlactataemia and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative.

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