Linked Life Data

21169382

Source:http://linkedlifedata.com/resource/pubmed/id/21169382

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-4-1
pubmed:databankReference
pubmed:abstractText
Glucose is considered essential for erythrocytic stages of the malaria parasite, Plasmodium falciparum. Importance of sugar and its permease for hepatic and sexual stages of Plasmodium, however, remains elusive. Moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. Here, we reveal that hexose transporter 1 (HT1) of Plasmodium berghei can transport glucose (K(m)~87 ?M), mannose (K(i)~93 ?M), fructose (K(i)~0.54 mM), and galactose (K(i)~5 mM) in Leishmania mexicana mutant and Xenopus laevis; and, therefore, is functionally equivalent to HT1 of P. falciparum (Glc, K(m)~175 ?M; Man, K(i)~276 ?M; Fru, K(i)~1.25 mM; Gal, K(i)~5.86 mM). Notably, a glucose analog, C3361, attenuated hepatic (IC(50)~15 ?M) and ookinete development of P. berghei. The PbHT1 could be ablated during intraerythrocytic stages only by concurrent complementation with PbHT1-HA or PfHT1. Together; these results signify that PbHT1 and glucose are required for the entire life cycle of P. berghei. Accordingly, PbHT1 is expressed in the plasma membrane during all parasite stages. To permit a high-throughput screening of PfHT1 inhibitors and their subsequent in vivo assessment, we have generated Saccharomyces cerevisiae mutant expressing codon-optimized PfHT1, and a PfHT1-dependent ?pbht1 parasite strain. This work provides a platform to facilitate the development of drugs against malaria, and it suggests a disease-control aspect by reducing parasite transmission.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1218-29
pubmed:meshHeading
pubmed-meshheading:21169382-Amino Acid Sequence, pubmed-meshheading:21169382-Animals, pubmed-meshheading:21169382-Antimalarials, pubmed-meshheading:21169382-Base Sequence, pubmed-meshheading:21169382-Fructose, pubmed-meshheading:21169382-Galactose, pubmed-meshheading:21169382-Glucose, pubmed-meshheading:21169382-Humans, pubmed-meshheading:21169382-Leishmania mexicana, pubmed-meshheading:21169382-Life Cycle Stages, pubmed-meshheading:21169382-Mannose, pubmed-meshheading:21169382-Mice, pubmed-meshheading:21169382-Molecular Sequence Data, pubmed-meshheading:21169382-Monosaccharide Transport Proteins, pubmed-meshheading:21169382-Plasmodium berghei, pubmed-meshheading:21169382-Plasmodium falciparum, pubmed-meshheading:21169382-Protozoan Proteins, pubmed-meshheading:21169382-Recombinant Proteins, pubmed-meshheading:21169382-Saccharomyces cerevisiae, pubmed-meshheading:21169382-Toxoplasma, pubmed-meshheading:21169382-Xenopus laevis
pubmed:year
2011
pubmed:articleTitle
A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.
pubmed:affiliation
Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural