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Plasmodium falciparum

Transport of purines and purine salvage pathway inhibitors by the Plasmodium falciparum equilibrative nucleoside transporter PfENT1.

November 18, 2009 - 12:51 -- Kabogo Ndegwa
Author(s): 
Paul M. Riegelhaupt, María B. Cassera, Richard F.G. Fröhlich, Keith Z. Hazleton, Jonathan J. Hefter, Vern L. Schramm, Myles H. Akabas
Reference: 
Molecular and Biochemical Parasitology, Volume 169, Issue 1, January 2010, Pages 40-49, doi:10.1016/j.molbiopara.2009.10.001

Plasmodium falciparum is a purine auxotroph. The transport of purine nucleosides and nucleobases from the host erythrocyte to the parasite cytoplasm is essential to support parasite growth. P. falciparum equilibrative nucleoside transporter 1 (PfENT1) is a major route for purine transport across the parasite plasma membrane. Malarial parasites are sensitive to inhibitors of purine salvage pathway enzymes. The immucillin class of purine nucleoside phosphorylase inhibitors and the adenosine analog, tubercidin, block growth of P. falciparum under in vitro culture conditions. We sought to determine whether these inhibitors utilize PfENT1 to gain access to the parasite cytosol.

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In Vitro Activities of Piperaquine, Lumefantrine, and Dihydroartemisinin in Kenyan Plasmodium falciparum Isolates and Polymorphisms in pfcrt and pfmdr1.

November 18, 2009 - 12:47 -- Patrick Sampao
Author(s): 
Leah Mwai, Steven M. Kiara, Abdi Abdirahman, Lewa Pole, Anja Rippert, Abdi Diriye, Pete Bull, Kevin Marsh, Steffen Borrmann, and Alexis Nzila
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5069-5073, Vol. 53, No. 12, doi:10.1128/AAC.00638-09

We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin in association with polymorphisms in pfcrt at codon 76 and pfmdr1 at codon 86, as well as with variations of the copy number of pfmdr1.

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Transcriptomic Profiling of the Saccharomyces cerevisiae Response to Quinine Reveals a Glucose Limitation Response Attributable to Drug-Induced Inhibition of Glucose Uptake

November 18, 2009 - 12:43 -- Patrick Sampao
Author(s): 
Sandra C. dos Santos, Sandra Tenreiro, Margarida Palma,Jorg Becker, and Isabel Sá-Correia.
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5213-5223, Vol. 53, No. 12, doi:10.1128/AAC.00794-09

Quinine has been employed in the treatment of malaria for centuries and is still used against severe Plasmodium falciparum malaria. However, its interactions with the parasite remain poorly understood and subject to debate. In this study, we used the Saccharomyces cerevisiae eukaryotic model to better understand quinine's mode of action and the mechanisms underlying the cell response to the drug.

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The dynamics of mutations associated with anti-malarial drug resistance in Plasmodium falciparum.

November 18, 2009 - 12:38 -- Kabogo Ndegwa
Author(s): 
Ananias A. Escalante, David L. Smith, Yuseob Kim.
Reference: 
Trends in Parasitology, Volume 25, Issue 12, December 2009, Pages 557-563, doi:10.1016/j.pt.2009.09.008

The evolution of resistance in Plasmodium falciparum against safe and affordable drugs such as chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) is a major global health threat. Investigating the dynamics of resistance against these antimalarial drugs will lead to approaches for addressing the problem of resistance in malarial parasites that are solidly based in evolutionary genetics and population biology. In this article, we discuss current developments in population biology modeling and evolutionary genetics.

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Mechanisms of Resistance; Characteristics of Genetic Hitchhiking around Dihydrofolate Reductase Gene Associated with Pyrimethamine Resistance in Plasmodium falciparum Isolates from India .

November 18, 2009 - 12:34 -- Patrick Sampao
Author(s): 
Vanshika Lumb, Manoj K. Das, Neeru Singh, Vas Dev, Wajihullah,4 and Yagya D. Sharma
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5173-5180, Vol. 53, No. 12, doi:10.1128/AAC.00045-09

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread across continents, causing the major hurdle of controlling malaria. Resistance is encoded mainly by point mutations in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) target genes. To study the origin and evolution of pyrimethamine resistance on the Indian subcontinent, microsatellite markers flanking the pfdhfr gene were mapped. Here we describe the characteristics of genetic hitchhiking around the pfdhfr gene among 190 P. falciparum isolates.

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Mechanisms of action; Role of Plasmodium falciparum Digestive Vacuole Plasmepsins in the Specificity and Antimalarial Mode of Action of Cysteine and Aspartic Protease Inhibitors

November 18, 2009 - 12:21 -- Patrick Sampao
Author(s): 
Pedro A. Moura, John B. Dame, and David A. Fidock
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 4968-4978, Vol. 53, No. 12, doi:10.1128/AAC.00882-09

Hemoglobin (Hb) degradation is essential for the growth of the intraerythrocytic stages of malarial parasites. This process, which occurs inside an acidic digestive vacuole (DV), is thought to involve the action of four aspartic proteases, termed plasmepsins (PMs). These enzymes have received considerable attention as potential antimalarial drug targets.

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Plasmodium falciparum exposure in utero, maternal age and parity influence the innate activation of foetal antigen presenting cells

November 10, 2009 - 12:58 -- Ingeborg van Schayk
Author(s): 
Nadine Fievet, Stefania Varani, Samad Ibitokou, Valerie Briand, Stephanie Louis, Rene-Xavier Perrin, Achille Massougbodji, Anne Hosmalin, Marita Troye-Blomberg, Philippe Deloron
Reference: 
Malaria Journal 2009, 8:251 (5 November 2009)

The findings support the view that placental parasitization is significantly associated with partial maturation of different dendritic cell subsets and also to slightly increased responses to TLR9 ligand in cord blood.

Comparison of Plasmodium falciparum allelic frequency distribution in different endemic settings by high-resolution genotyping

November 10, 2009 - 12:40 -- Ingeborg van Schayk
Author(s): 
Sonja Schoepflin, Francesca Valsangiacomo, Enmoore Lin, Benson Kiniboro, Ivo Mueller, Ingrid Felger
Reference: 
Malaria Journal 2009, 8:250 (30 October 2009)

A description of allele frequencies of two polymorphic P. falciparum surface antigens from two sites of varying transmission intensity, Papua New Guinea and Tanzania. It confirms previous reports of a higher mean multiplicity of infection and increased genetic diversity in areas of higher endemicity.

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