Plasmodium Permeomics: Membrane Transport Proteins in the Malaria Parasite

Kirk, Kiaran; Martin, R. L.; Bröer, Stefan; Howitt, Susan; Saliba, Kevin J.

doi:10.1007/3-540-29088-5_13

Cited by 13 publications

(7 citation statements)

References 129 publications

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“…Infection of erythrocytes by P. falciparum is accompanied by major changes in the erythrocyte membrane, which result in increased permeability to a large number of substrates, many of which are essential nutrients such as sugars, purine nucleosides and nucleobases, vitamins, and amino acids (28,29). Once inside the red blood cytoplasm, these precursors are transported inside the parasite by specific permeases expressed on the parasite plasma membrane (30)(31)(32). The selective delivery of the conjugates into infected erythrocytes but not uninfected erythrocytes, suggest that they may likely use the new permeation pathway (33) on the red blood cell membrane and possibly an oligopeptide permease on the parasite plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum

Augagneur

Wesolowski

Tae

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Unique peptide-morpholino oligomer (PMO) conjugates have been designed to bind and promote the cleavage of specific mRNA as a tool to inhibit gene function and parasite growth. The new conjugates were validated using the P. falciparum gyrase mRNA as a target (PfGyrA). Assays in vitro demonstrated a selective degradation of the PfGyrA mRNA directed by the external guide sequences, which are morpholino oligomers in the conjugates. Fluorescence microscopy revealed that labeled conjugates are delivered into Plasmodium-infected erythrocytes during all intraerythrocytic stages of parasite development. Consistent with the expression of PfGyrA in all stages of parasite development, proliferation assays showed that these conjugates have potent antimalarial activity, blocking early development, maturation, and replication of the parasite. The conjugates were equally effective against drug sensitive and resistant P. falciparum strains. The potency, selectivity, and predicted safety of PMO conjugates make this approach attractive for the development of a unique class of target-specific antimalarials and for largescale functional analysis of the malarial genome.RNase P | nuclease resistance

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Section: Discussionmentioning

confidence: 99%

Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum

Augagneur

Wesolowski

Tae

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Upon invading an erythrocyte the parasite induces major modifications to the host cell to permit the directed exchange of metabolites [reviewed in (Kirk et al, 2005)]. New permeability pathways are induced on the host cell surface to enhance the influx and efflux of specific compounds.…”

Section: Introductionmentioning

confidence: 99%

Host-Parasite Interactions Revealed by Plasmodium falciparum Metabolomics

Olszewski

Morrisey

Wilinski

et al. 2009

Cell Host & Microbe

256

303

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Summary Intracellular pathogens have devised mechanisms to exploit their host cells to ensure their survival and replication. The malaria parasite Plasmodium falciparum relies on an exchange of metabolites with the host for proliferation. We describe the first mass spectrometry-based metabolomic analysis of the parasite throughout its 48-hour intraerythrocytic developmental cycle. Our results reveal a general modulation of metabolite levels by the parasite, with numerous metabolites varying in phase with the developmental cycle. Others differed from uninfected cells irrespective of the developmental stage. Among these was extracellular arginine, which was specifically converted to ornithine by the parasite. To identify the biochemical basis for this effect, we disrupted the plasmodium arginase gene in the rodent malaria model P. berghei. These parasites were viable but did not convert arginine to ornithine. Our results suggest that systemic arginine depletion by the parasite may be a factor in human malarial hypoargininemia associated with cerebral malaria pathogenesis.

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“…The confirmation of the existence of two MRP-like proteins coded in the P. falciparum genome, as compared with the typical presence of only one in rodent Plasmodia (Gonzalez-Pons et al, 2009;Koenderink et al, 2010) has been supported upon a number of detailed in silico data mining works (Bozdech and Ginsburg, 2004;Kirk et al, 2005;Martin et al, 2005Martin et al, , 2009Kaviche et al, 2009).…”

Section: Plasmodium Falciparum Harbors Two Multidrug Resistance Proteinsmentioning

confidence: 96%

Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

Gil

Fançony²

2021

Front. Pharmacol.

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The capacity of the lethal Plasmodium falciparum parasite to develop resistance against anti-malarial drugs represents a central challenge in the global control and elimination of malaria. Historically, the action of drug transporters is known to play a pivotal role in the capacity of the parasite to evade drug action. MRPs (Multidrug Resistance Protein) are known in many phylogenetically diverse groups to be related to drug resistance by being able to handle a large range of substrates, including important endogenous substances as glutathione and its conjugates. P. falciparum MRPs are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment. Information on P. falciparum MRPs is scattered in the literature, with no specialized review available. We herein address this issue by reviewing the present state of knowledge.

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Plasmodium Permeomics: Membrane Transport Proteins in the Malaria Parasite

Cited by 13 publications

References 129 publications

Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum

Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum

Host-Parasite Interactions Revealed by Plasmodium falciparum Metabolomics

Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

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