Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6772
pubmed:dateCreated
2000-3-21
pubmed:abstractText
Throughout the latter half of this century, the development and spread of resistance to most front-line antimalarial compounds used in the prevention and treatment of the most severe form of human malaria has given cause for grave clinical concern. Polymorphisms in pfmdr1, the gene encoding the P-glycoprotein homologue 1 (Pgh1) protein of Plasmodium falciparum, have been linked to chloroquine resistance; Pgh1 has also been implicated in resistance to mefloquine and halofantrine. However, conclusive evidence of a direct causal association between pfmdr1 and resistance to these antimalarials has remained elusive, and a single genetic cross has suggested that Pgh1 is not involved in resistance to chloroquine and mefloquine. Here we provide direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine. The same mutations influence parasite resistance towards chloroquine in a strain-specific manner and the level of sensitivity to the structurally unrelated compound, artemisinin. This has important implications for the development and efficacy of future antimalarial agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters, http://linkedlifedata.com/resource/pubmed/chemical/Antimalarials, http://linkedlifedata.com/resource/pubmed/chemical/Artemisinins, http://linkedlifedata.com/resource/pubmed/chemical/Chloroquine, http://linkedlifedata.com/resource/pubmed/chemical/Mefloquine, http://linkedlifedata.com/resource/pubmed/chemical/Phenanthrenes, http://linkedlifedata.com/resource/pubmed/chemical/Protozoan Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Quinine, http://linkedlifedata.com/resource/pubmed/chemical/Sesquiterpenes, http://linkedlifedata.com/resource/pubmed/chemical/Verapamil, http://linkedlifedata.com/resource/pubmed/chemical/artemisinine, http://linkedlifedata.com/resource/pubmed/chemical/halofantrine, http://linkedlifedata.com/resource/pubmed/chemical/mdr gene protein, Plasmodium
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
403
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
906-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.
pubmed:affiliation
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't