Is the Resistance Transporter Gene pfcrt Linked with Susceptibility of Plasmodium falciparum to Chloroquine

Recent studies have definitively demonstrated a link between mutations in the gene pfcrt and resistance to the antimalarial chloroquine (CQ) in Plasmodium falciparum. Although these mutations are predictive of CQ resistance they are not quantitatively predictive of the degree of resistance. We had undertaken analysis of a total of 95 recently adapted P. falciparum isolates from Thailand. Parasites had been characterized for their drug susceptibility phenotypes and genotypes with respect to pfcrt. From the original 95 isolates, 20 were selected for complete pfcrt sequence analysis. Almost all of the parasites characterized carried the previously reported mutations K76T, A220S, Q271E, N326S, I356T and R371I. On complete sequencing, isolates were identified with novel mutations at K76A and E198K. The isolates carrying E198K were less resistant to CQ than those that were not. Data from the present study suggested that other genes may also contribute to the degree of resistance once the resistance phenotype is established through mutations in pfcrt gene.