Linked Life Data

21464256

Source:http://linkedlifedata.com/resource/pubmed/id/21464256

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-19
pubmed:abstractText
Due to their rapid, potent action on young and mature intraerythrocytic stages, artemisinin derivatives are central to drug combination therapies for Plasmodium falciparum malaria. However, the evidence for emerging parasite resistance/tolerance to artemisinins in southeast Asia is of great concern. A better understanding of artemisinin-related drug activity and resistance mechanisms is urgently needed. A recent transcriptome study of parasites exposed to artesunate led us to identify a series of genes with modified levels of expression in the presence of the drug. The gene presenting the largest mRNA level increase, Pf10_0026 (PArt), encoding a hypothetical protein of unknown function, was chosen for further study. Immunodetection with PArt-specific sera showed that artesunate induced a dose-dependent increase of the protein level. Bioinformatic analysis showed that PArt belongs to a Plasmodium-specific gene family characterized by the presence of a tryptophan-rich domain with a novel hidden Markov model (HMM) profile. Gene disruption could not be achieved, suggesting an essential function. Transgenic parasites overexpressing PArt protein were generated and exhibited tolerance to a spike exposure to high doses of artesunate, with increased survival and reduced growth retardation compared to that of wild-type-treated controls. These data indicate the involvement of PArt in parasite defense mechanisms against artesunate. This is the first report of genetically manipulated parasites displaying a stable and reproducible decreased susceptibility to artesunate, providing new possibilities to investigate the parasite response to artemisinins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-6596
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2576-84
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Artesunate tolerance in transgenic Plasmodium falciparum parasites overexpressing a tryptophan-rich protein.
pubmed:affiliation
Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, Département de Parasitologie Mycologie, CNRS, URA2581, F-75015 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't