Immunogenic Antigens Common to Plasmodium knowlesi and Plasmodium falciparum Are Expressed on the Surface of Infected Erythrocytes

1982 ◽  
Vol 68 (2) ◽  
pp. 185 ◽  
Author(s):  
Rupert Schmidt-Ullrich ◽  
Louis H. Miller ◽  
Donald F. H. Wallach ◽  
John Lightholder
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Knowlesi

scholarly journals Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum

2022 ◽  
Vol 11 ◽  
Author(s):  
Laís Pessanha de Carvalho ◽  
Sara Groeger-Otero ◽  
Andrea Kreidenweiss ◽  
Peter G. Kremsner ◽  
Benjamin Mordmüller ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Knowlesi ◽  
Rapid Onset ◽  
Multidrug Resistant ◽  
Antiplasmodial Activity ◽  
Onset Of Action ◽  
Streptomyces Antibioticus ◽  
Life Cycle Stages ◽  
Almost All

Boromycin is a boron-containing macrolide antibiotic produced by Streptomyces antibioticus with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. In vitro antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against Plasmodium falciparum and the zoonotic Plasmodium knowlesi. In contrast to tetracyclines, boromycin rapidly killed asexual stages of both Plasmodium species already at low concentrations (~ 1 nM) including multidrug resistant P. falciparum strains (Dd2, K1, 7G8). In addition, boromycin was active against P. falciparum stage V gametocytes at a low nanomolar range (IC50: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.

scholarly journals Use of a highly specific kinase inhibitor for rapid, simple and precise synchronization of Plasmodium falciparum and Plasmodium knowlesi asexual blood-stage parasites

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235798
Author(s):  
Margarida Ressurreição ◽  
James A. Thomas ◽  
Stephanie D. Nofal ◽  
Christian Flueck ◽  
Robert W. Moon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Kinase Inhibitor ◽  
Plasmodium Knowlesi ◽  
Blood Stage ◽  
Asexual Blood Stage ◽  
Specific Kinase Inhibitor

scholarly journals Use of a highly specific kinase inhibitor for rapid, simple and precise synchronization of Plasmodium falciparum and Plasmodium knowlesi asexual stage parasites

2020 ◽  
Author(s):  
Margarida Ressurreição ◽  
James A. Thomas ◽  
Stephanie D. Nofal ◽  
Christian Flueck ◽  
Robert W. Moon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Host Cell ◽  
Kinase Inhibitor ◽  
Plasmodium Knowlesi ◽  
Morphological Changes ◽  
Specific Inhibitor ◽  
Blood Stage ◽  
Dependent Manner ◽  
Asexual Blood Stage ◽  
Stage Of Development

ABSTRACTDuring the course of the asexual erythrocytic stage of development, Plasmodium spp. parasites undergo a series of morphological changes and induce alterations in the host cell. At the end of this stage, the parasites exit the host cell, after which the progeny invade a new host cell. These processes are rapid and occur in a time-dependent manner. Of particular importance, egress and invasion of erythrocytes by the parasite are difficult to capture in an unsynchronized culture, or even a culture that has been synchronized to within hours. Therefore, precise synchronization of parasite cultures is of paramount importance for the investigation of these processes. Here we describe a method for synchronizing Plasmodium falciparum and Plasmodium knowlesi asexual blood stage parasites with ML10, a highly specific inhibitor of the cGMP-dependent protein kinase (PKG) that arrests parasite growth approximately 15 minutes prior to egress. This inhibitor allows parasite cultures to be synchronized to within minutes, with a simple wash step. Furthermore, we show that parasites remain viable for several hours after becoming arrested by the compound and that ML10 has advantages over the previously used PKG inhibitor Compound 2. Here, we demonstrate that ML10 is an invaluable tool for the study of Plasmodium spp. asexual blood stage biology and for the routine synchronization of P. falciparum and P. knowlesi cultures.

scholarly journals Cytoadherence Properties of Plasmodium knowlesi-Infected Erythrocytes

2022 ◽  
Vol 12 ◽  
Author(s):  
Wenn-Chyau Lee ◽  
Shahhaziq Shahari ◽  
Samantha Yee Teng Nguee ◽  
Yee-Ling Lau ◽  
Laurent Rénia
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Culture Supernatant ◽  
Plasmodium Knowlesi ◽  
Dependent Manner ◽  
Zoonotic Malaria ◽  
Different Types ◽  
Severe Pathology ◽  
Serum Dependent ◽  
The Brain

Plasmodium knowlesi is responsible for zoonotic malaria infections that are potentially fatal. While the severe pathology of falciparum malaria is associated with cytoadherence phenomena by Plasmodium falciparum-infected erythrocytes (IRBC), information regarding cytoadherence properties of P. knowlesi-IRBC remained scarce. Here, we characterized the cytoadherence properties of RBC infected with the laboratory-adapted P. knowlesi A1-H.1 strain. We found that late-stage IRBC formed rosettes in a human serum-dependent manner, and rosettes hampered IRBC phagocytosis. IRBC did not adhere much to unexposed (unstimulated) human endothelial cell lines derived from the brain (hCMEC/D3), lungs (HPMEC), and kidneys (HRGEC). However, after being “primed” with P. knowlesi culture supernatant, the IRBC-endothelial cytoadherence rate increased in HPMEC and HRGEC, but not in hCMEC/D3 cells. Both endothelial cytoadherence and rosetting phenomena were abrogated by treatment of P. knowlesi-IRBC with trypsin. We also found that different receptors were involved in IRBC cytoadherence to different types of endothelial cells. Although some of the host receptors were shared by both P. falciparum- and P. knowlesi-IRBC, the availability of glycoconjugates on the receptors might influence the capacity of P. knowlesi-IRBC to cytoadhere to these receptors.

scholarly journals Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts.

1980 ◽  
Vol 151 (4) ◽  
pp. 790-798 ◽  
Author(s):  
L H Miller ◽  
J G Johnson ◽  
R Schmidt-Ullrich ◽  
J D Haynes ◽  
D F Wallach ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Knowlesi ◽  
Cross Reactivity ◽  
Cross Reaction ◽  
Surface Proteins ◽  
Major Protein ◽  
The Cross

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.

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