Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria.
Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.
Nomura
T
T
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA.
Carlton
J M
JM
Baird
J K
JK
del Portillo
H A
HA
Fryauff
D J
DJ
Rathore
D
D
Fidock
D A
DA
Su
X
X
Collins
W E
WE
McCutchan
T F
TF
Wootton
J C
JC
Wellems
T E
TE
D000595:Amino Acid Sequence; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D003062:Codon; D004023:Dictyostelium / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D016415:Sequence Alignment
D003062:Codon; D018832:Molecular Chaperones; C112806:prefoldin; D002738:Chloroquine