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 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 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 Protein trafficking in Plasmodium falciparum-infected red cells and impact of the expansion of exported protein families

Parasitology ◽  
2014 ◽  
Vol 141 (12) ◽  
pp. 1533-1543 ◽  
Author(s):  
SURENDRA K. PRAJAPATI ◽  
RICHARD CULLETON ◽  
OM P. SINGH
Keyword(s):  
Plasmodium Falciparum ◽  
Host Cell ◽  
Protein Trafficking ◽  
Malaria Parasite ◽  
Functional Characterization ◽  
Gene Families ◽  
Red Cells ◽  
Protein Families ◽  
The Impact ◽  
Export Signal

SUMMARYErythrocytes are extensively remodelled by the malaria parasite following invasion of the cell. Plasmodium falciparum encodes numerous virulence-associated and host-cell remodelling proteins that are trafficked to the cytoplasm, the cell membrane and the surface of the infected erythrocyte. The export of soluble proteins relies on a sequence directing entry into the secretory pathways in addition to an export signal. The export signal consisting of five amino acids is termed the Plasmodium export element (PEXEL) or the vacuole transport signal (VTS). Genome mining studies have revealed that PEXEL/VTS carrying protein families have expanded dramatically in P. falciparum compared with other malaria parasite species, possibly due to lineage-specific expansion linked to the unique requirements of P. falciparum for host-cell remodelling. The functional characterization of such genes and gene families may reveal potential drug targets that could inhibit protein trafficking in infected erythrocytes. This review highlights some of the recent advances and key knowledge gaps in protein trafficking pathways in P. falciparum-infected red cells and speculates on the impact of exported gene families in the trafficking pathway.

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 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 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 Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

Blood ◽  
2018 ◽  
Vol 131 (11) ◽  
pp. 1234-1247 ◽  
Author(s):  
Souvik Bhattacharjee ◽  
Isabelle Coppens ◽  
Alassane Mbengue ◽  
Niraja Suresh ◽  
Mehdi Ghorbal ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Artemisinin Resistance ◽  
Red Cells ◽  
Red Cell ◽  
Malaria Parasites ◽  
Key Points

Key Points Vesicular system causing artemisinin resistance modifies malaria parasites and host red cells.

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.

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

Abstract 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.

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