ABCMdb

PMID: 11512154

Peel SA
The ABC transporter genes of Plasmodium falciparum and drug resistance.
Drug Resist Updat. 2001 Feb;4(1):66-74., [PubMed]

Sentences

No. Mutations Sentence Comment

35 ABCB1 p.Ala220Ser Sequence analysis of chloroquine resistant parasites from diverse geographic regions (Asia,Africa,SouthAmerica) revealed a polymorphic gene, which in all cases included intra-allelic mutations Lys 76Thr and Ala 220Ser , as well as mutations in two to six additional codons. Login to comment 52 ABCB4 p.Asn1042Asp Expression of the 7G8 chloroquine-resistance mutations, Cys-1034 and Asp-1042, implicated in chloroquine resistance, resulted in loss-of-function mutants (i.e. abolished the mating phenotype), suggesting that these genetic polymorphisms alter transport function.82 It should be noted that a similar study analyzing quinoline antimalarials in a ste6 mutant strain was recently withdrawn from publication due to contamination of transformants with wild-type ste6 sequences.86,87 The advance of stable transgene transfection of in-vitro cultured P. falciparum has permitted in vivo analysis of the functional significance of Pgh1.88 Elegant experiments by Reed et al.89 have offered the first definitive evidence that polymorphisms in pfmdr 1 can confer resistance to mefloquine, halofantrine, and quinine.These authors also demonstrated that polymorphisms of pfmdr 1 can modulate levels of chloroquine resistance in a strain-specific manner, as well as modulate sensitivity to the structurally unrelated antimalarial artemisinin Three of the 7G8 intra-alleles Ser 1034Cys , Asn 1042Asp , Asp 1246Tyr implicated in chloroquine resistance were examined by allelic exchange of the endogenous pfmdr 1 locus. Login to comment