scholarly journals Visualization of Malaria Parasites in the Skin Using the Luciferase Transgenic Parasite, Plasmodium berghei

2015 ◽  
Vol 43 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Hiroyuki Matsuoka ◽  
Hiroyuki Tomita ◽  
Ryuta Hattori ◽  
Meiji Arai ◽  
Makoto Hirai
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Parasites ◽  
Transgenic Parasite

scholarly journals In VitroandIn VivoAntimalarial Efficacies of Optimized Tetracyclines

2013 ◽  
Vol 57 (7) ◽  
pp. 3131-3136 ◽  
Author(s):  
Michael P. Draper ◽  
Beena Bhatia ◽  
Haregewein Assefa ◽  
Laura Honeyman ◽  
Lynne K. Garrity-Ryan ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Inhibitory Concentration ◽  
New Drugs ◽  
Malaria Parasites ◽  
Content Type ◽  
Antimalarial Agents ◽  
Content Model ◽  
Safety Margins ◽  
Malaria Model

ABSTRACTWith increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. We synthesized 18 novel 7-position modified tetracycline derivatives and screened them for activity against cultured malaria parasites. Compounds with potentin vitroactivity and other favorable drug properties were further tested in a rodent malaria model. Ten compounds inhibited the development of culturedPlasmodium falciparumwith a 50% inhibitory concentration (IC50) after 96 h of incubation of <30 nM, demonstrating activity markedly superior to that of doxycycline (IC50at 96 h of 320 nM). Most compounds showed little mammalian cell cytotoxicity and no evidence ofin vitrophototoxicity. In a murinePlasmodium bergheimodel, 13 compounds demonstrated improved activity relative to that of doxycycline. In summary, 7-position modified tetracyclines offer improved activity against malaria parasites compared to doxycycline. Optimized compounds may allow lower doses for treatment and chemoprophylaxis. If safety margins are adequate, dosing in children, the group at greatest risk for malaria in countries in which it is endemic, may be feasible.

Isolation of Plasmodium berghei (Malaria) Parasites by Ammonium Chloride Lysis of Infected Erythrocytes

1971 ◽  
Vol 233 (43) ◽  
pp. 260-261 ◽  
Author(s):  
W. J. MARTIN ◽  
J. FINERTY ◽  
A. ROSENTHAL
Keyword(s):  
Ammonium Chloride ◽  
Plasmodium Berghei ◽  
Malaria Parasites

Multiple antigen constructs (MACs): induction of sterile immunity against sporozoite stage of rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii

Vaccine ◽  
1997 ◽  
Vol 15 (5) ◽  
pp. 482-488 ◽  
Author(s):  
R.C. Reed ◽  
V. Louis-Wileman ◽  
E.V. Cosmai ◽  
S. Fang ◽  
D.L. Jue ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Plasmodium Yoelii ◽  
Malaria Parasites ◽  
Rodent Malaria ◽  
Multiple Antigen

scholarly journals Antibody-mediated elimination of malaria parasites (plasmodium berghei) in vivo.

1975 ◽  
Vol 12 (2) ◽  
pp. 339-345 ◽  
Author(s):  
J Hamburger ◽  
J P Kreier
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Parasites

scholarly journals Dihydroquinazolinone Inhibitors of Proliferation of Blood and Liver Stage Malaria Parasites

2013 ◽  
Vol 58 (3) ◽  
pp. 1516-1522 ◽  
Author(s):  
Emily R. Derbyshire ◽  
Jaeki Min ◽  
W. Armand Guiguemde ◽  
Julie A. Clark ◽  
Michele C. Connelly ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Mammalian Cells ◽  
Blood Stage ◽  
Malaria Parasites ◽  
Liver Stage ◽  
Content Type ◽  
Minimal Toxicity ◽  
Structure Activity ◽  
Further Development

ABSTRACTDrugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. Evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds—dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles—with promising activity against the liver stage. Focused structure-activity studies on the dihydroquinazolinone scaffold revealed several molecules with excellent potency against both blood and liver stages. One promising early lead with dual activity is 2-(p-bromophenyl)-3-(2-(diethylamino)ethyl)-2,3-dihydroquinazolin-4(1H)-one with 50% effective concentrations (EC50s) of 0.46 μM and 0.34 μM against liver stagePlasmodium bergheiANKA and blood stagePlasmodium falciparum3D7 parasites, respectively. Structure-activity relationships revealed that liver stage activity for this compound class requires a 3-dialkyl amino ethyl group and is abolished by substitution at theortho-position of the phenyl moiety. These compounds have minimal toxicity to mammalian cells and are thus attractive compounds for further development.

scholarly journals Ca2+ signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG

2021 ◽  
Vol 7 (13) ◽  
pp. eabe5396
Author(s):  
Aurélia C. Balestra ◽  
Konstantinos Koussis ◽  
Natacha Klages ◽  
Steven A. Howell ◽  
Helen R. Flynn ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Calcium Channels ◽  
Plasmodium Berghei ◽  
Disease Transmission ◽  
Calcium Mobilization ◽  
Dependent Protein Kinase ◽  
Malaria Parasites ◽  
Cgmp Dependent Protein Kinase ◽  
Intracellular Calcium Mobilization ◽  
Dependent Protein

Calcium signaling regulated by the cGMP-dependent protein kinase (PKG) controls key life cycle transitions in the malaria parasite. However, how calcium is mobilized from intracellular stores in the absence of canonical calcium channels in Plasmodium is unknown. Here, we identify a multipass membrane protein, ICM1, with homology to transporters and calcium channels that is tightly associated with PKG in both asexual blood stages and transmission stages. Phosphoproteomic analyses reveal multiple ICM1 phosphorylation events dependent on PKG activity. Stage-specific depletion of Plasmodium berghei ICM1 prevents gametogenesis due to a block in intracellular calcium mobilization, while conditional loss of Plasmodium falciparum ICM1 is detrimental for the parasite resulting in severely reduced calcium mobilization, defective egress, and lack of invasion. Our findings suggest that ICM1 is a key missing link in transducing PKG-dependent signals and provide previously unknown insights into atypical calcium homeostasis in malaria parasites essential for pathology and disease transmission.

scholarly journals Rapid inducible protein displacement in Plasmodium in vivo and in vitro using knocksideways technology

2017 ◽  
Vol 2 ◽  
pp. 18 ◽  
Author(s):  
Katie R. Hughes ◽  
Andy P. Waters
Keyword(s):  
Plasmodium Berghei ◽  
Genetic Manipulation ◽  
Live Imaging ◽  
Malaria Parasites ◽  
Essential Proteins ◽  
Inducible Protein ◽  
Fluorescent Tags ◽  
Proof Of Principle

A deeper understanding of the biology of the Plasmodium parasite is essential in order to identify targets for interventions, with the ultimate aim of eliminating malaria. Determining the function(s) of essential proteins in Plasmodium has, until recently, been hampered by the lack of efficient conditional systems to abrogate proteins. We report the adaptation of a conditional technology, knocksideways (KS), for use in Plasmodium berghei, which can potentially rapidly inactivate proteins of interest through relocalisation. The system is induced using rapamycin, which allows for KS both in vitro and in vivo and is effective more rapidly than any other reported system. KS utilises pairs of fluorescent tags that facilitate live imaging and allows for rapid confirmation of efficient protein redistribution on live parasites, allowing for streamlined workflows. We demonstrate the characteristics of the system using transgenically expressed cytoplasmic GFP and provide proof of principle by inducibly redistributing a number of proteins with different native, subcellular locations.  We also demonstrate that KS can be applied to both mammalian and insect stages of Plasmodium. KS expands the range of (conditional) technologies for genetic manipulation of malaria parasites and offers the potential to be further developed for medium throughput phenotype screens.

A comparative account of the effects of betamethasone on mice infected with Plasmodium vinckei chabaudi and Plasmodium berghei yoelii

Parasitology ◽  
1974 ◽  
Vol 68 (1) ◽  
pp. 19-26 ◽  
Author(s):  
F. E. G. Cox
Keyword(s):  
Plasmodium Berghei ◽  
Immunological Response ◽  
Malaria Parasites ◽  
Antibody Levels ◽  
Reticulocyte Production ◽  
Plasmodium Vinckei

The malaria parasites, Plasmodium berghei yoelii and P. vinckei chabaudi, run comparable courses of infection in mice. When mice were treated with betamethasone infections with P. v. chabaudi were enhanced while those of P. b. yoelii were depressed. Antibody levels in betamethasone-treated mice infected with either P. b. yoelii or P. v. chabaudi were depressed to similar extents. The differences in parasitaemias in the two different infections are attributed to the suppression of reticulocyte production by betamethasone. P. b. yoelii preferentially invades reticulocytes and the patterns of parasitaemia follow the level of reticulocytes in the blood. P. v. chabaudi has no preference for reticulocytes and the pattern of parasitaemia is influenced by the depressed immunological response of the host.

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