Pfcrt

Pfcrt stands for Plasmodium falciparum chloroquine resistance transporter and refers to a gene in the malaria parasite that encodes a membrane transporter protein located on the digestive vacuole membrane of Plasmodium falciparum. The gene is a major determinant of chloroquine resistance and is widely used as a molecular marker in resistance surveillance.

The PfCRT protein is about 427 amino acids long and is predicted to contain 10 transmembrane helices, placing it in the drug/metabolite transporter superfamily. The pfcrt gene is located on chromosome 7 of the P. falciparum genome. The wild-type transporter participates in normal substrate movement across the digestive vacuole membrane, whereas specific mutations alter its function.

Mutations in pfcrt are linked to the chloroquine resistance phenotype. The most notable change is the substitution of lysine by threonine at residue 76 (K76T), which is strongly associated with resistance. Additional substitutions at other codons, such as 72–75 and 220, give rise to distinct haplotypes, including CVIET and CVMNK, which vary by geographic region and influence resistance levels and drug response.

Epidemiologically, pfcrt mutations emerged during widespread chloroquine use and spread globally with parasite populations. Following changes in antimalarial policy and reduced chloroquine use in some areas, there have been reports of partial restoration of chloroquine sensitivity in certain regions, though pfcrt mutations often persist. PfCRT remains a key target in research on overcoming drug resistance, and pfcrt haplotypes are routinely monitored to track resistance dynamics and guide treatment policies.