Limited genetic diversity of the Plasmodium falciparum aquaglyceroporin gene.
In Plasmodium falciparum small solutes like water, ammonium, glycerol and others are transported by a parasite-encoded channel into the parasite. The gene encoding this channel is termed P. falciparum aquaglyceroporin (PfAQP) and is a single-copy gene and highly homologous to other aquaporins from other protozoa. Aquaporins are considered to be attractive targets for drug treatment and more so since the human and parasite aquaporins show considerable sequence differences. To investigate whether PfAQP may be suitable as a conserved target for potential aquaporin blocking agents we determined the DNA sequences of PfAQP from 65 parasite strains, either from in vitro cultured laboratory strains or from parasites obtained in an malaria-endemic region of Gabon. Only two non-synonymous mutations were found and functionally tested by a methylamine efflux assay. The efflux activity of all variants tested was similar. The lack of functionally variability suggests an invariable protein core, which may restrict parasite populations from evading therapeutic pressure if PfAQP inhibitors will be found.
Bahamontes-Rosa
Noemí
N
University of Tübingen, Department of Parasitology, Tübingen, Germany.
Wu
Binghua
B
Beitz
Eric
E
Kremsner
Peter G
PG
Kun
Jürgen F J
JF
D000595:Amino Acid Sequence; D000818:Animals; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D005681:Gabon; D014644:Genetic Variation; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008744:Methylamines / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D018272:Porins / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
D016054:DNA, Protozoan; D008744:Methylamines; C449801:PfAQP protein, Plasmodium falciparum; D018272:Porins; D015800:Protozoan Proteins; C027451:methylamine