Transport processes in Plasmodium falciparum-infected erythrocytes: potential as new drug targets

Krishna, Sanjeev; Eckstein-Ludwig, Ursula; Joët, Thierry; Uhlemann, Anne‐Catrin; Morin, Christophe; Webb, R.P.; Woodrow, Charles J.; Kun, Jürgen F. J.; Kremsner, Peter G.

doi:10.1016/s0020-7519(02)00185-6

Cited by 24 publications

(20 citation statements)

References 36 publications

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“…It is a single-copy gene with no close paralogues in the fully sequenced falciparum genome (5), and there is no variation in derived amino acid sequence of PfHT in laboratory and field isolates that we have studied (6). However, identification of a specific inhibitor of PfHT will only validate this transporter as a drug target if it also kills parasites.…”

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confidence: 99%

Validation of the hexose transporter of Plasmodium falciparum as a novel drug target

Joët

Eckstein-Ludwig

Morin

et al. 2003

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

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Chemotherapy of malaria parasites is limited by established drug resistance and lack of novel targets. Intraerythrocytic stages of Plasmodium falciparum are wholly dependent on host glucose for energy. Glucose uptake is mediated by a parasite-encoded facilitative hexose transporter (PfHT). We report that O-3 hexose derivatives inhibit uptake of glucose and fructose by PfHT when expressed in Xenopus oocytes. Selectivity of these derivatives for PfHT is confirmed by lack of inhibition of hexose transport by the major mammalian glucose and fructose transporters (Gluts) 1 and 5. A long chain O-3 hexose derivative is the most effective inhibitor of PfHT and also kills P. falciparum when it is cultured in medium containing either glucose or fructose as a carbon source. To extend our observations to the second most important human malarial pathogen, we have cloned and expressed the Plasmodium vivax orthologue of PfHT, and demonstrate inhibition of glucose uptake by the long chain O-3 hexose derivative. Furthermore, multiplication of Plasmodium berghei in a mouse model is significantly reduced by the O-3 derivative. Our robust expression system conclusively validates PfHT as a novel drug target and is an important step in the development of novel antimalarials directed against membrane transport proteins.Xenopus oocyte ͉ malaria ͉ antimalarial ͉ glucose analogues ͉ transport

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mentioning

confidence: 99%

Validation of the hexose transporter of Plasmodium falciparum as a novel drug target

Joët

Eckstein-Ludwig

Morin

et al. 2003

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

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134

151

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“…Resistance to these drugs is now so high as to render them "virtually useless [12]. These ineffective drugs continue to be used despite the spectacular levels of resistance, leading to www.intechopen.com Malaria Parasites 8 increased treatment failure.…”

Section: Drug and Vector Resistancesmentioning

confidence: 99%

Malaria, a Pending Problem in Sub-Saharan Africa

Okwa¹

2012

Malaria Parasites

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“…[1] P. falciparum infection induces alterations in the transport properties of infected erythrocytes that have recently been deÞ ned using electrophysiological techniques. [2] Mechanisms responsible for transport of substrates into intraerythrocytic parasites have also been clariÞ ed by studies of three substrate-speciÞ c (hexose, nucleoside and aquaglyceroporin) parasite plasma membrane transporters. [2] Aquaglyceroporin is a subclass of aquaporin water channels.…”

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confidence: 99%

“…[2] Mechanisms responsible for transport of substrates into intraerythrocytic parasites have also been clariÞ ed by studies of three substrate-speciÞ c (hexose, nucleoside and aquaglyceroporin) parasite plasma membrane transporters. [2] Aquaglyceroporin is a subclass of aquaporin water channels. [3] Aquaglyceroporins are also able to transport glycerol and perhaps urea and other small solutes.…”

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confidence: 99%

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Identification of transmembrane region and orientation of aquaglyceroporin of <i> Plasmodium falciparum</i>

Wiwanitkit¹

2008

Indian J Med Microbiol

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Aquaglyceroporin is a subclass of aquaporin water channels. This protein is also a focused potential drug target for falciparum malaria. However, the knowledge about the structure of this protein is limited. In this communication, the author performed a study to determine the transmembrane region and orientation of aquaglyceroporin of Plasmodium falciparum. According to this study, six transmembrane regions of aquaglyceroporin of P. falciparum can be identiÞ ed. These regions can be the focused target for future drug development.

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Transport processes in Plasmodium falciparum-infected erythrocytes: potential as new drug targets

Cited by 24 publications

References 36 publications

Validation of the hexose transporter of Plasmodium falciparum as a novel drug target

Validation of the hexose transporter of Plasmodium falciparum as a novel drug target

Malaria, a Pending Problem in Sub-Saharan Africa

Identification of transmembrane region and orientation of aquaglyceroporin of <i> Plasmodium falciparum</i>

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