Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents.

ABSTRACT: Chloroquine resistance in Plasmodium falciparum is primarily conferred by mutations in pfcrt. Parasites resistant to chloroquine can display hypersensitivity to other antimalarials; however, the patterns of crossresistance are complex, and the genetic basis has remained elusive. We show that stepwise selection for resistance to amantadine or halofantrine produced previously unknown pfcrt mutations (including S163R), which were associated with a loss of verapamil-reversible chloroquine resistance. This was accompanied by restoration of efficient chloroquine binding to hematin in these selected lines. This S163R mutation provides insight into a mechanism by which PfCRT could gate the transport of protonated chloroquine through the digestive vacuole membrane. Evidence for the presence of this

SUBMITTER: Johnson DJ 

PROVIDER: S-EPMC2943419 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature