The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance

Chloroquine resistance in the human malaria parasite, Plasmodium falciparum, arises from decreased accumulation of the drug in the 'digestive vacuole' of the parasite, an acidic compartment in which chloroquine exerts its primary toxic effect. It has been proposed that changes in the pH of the digestive vacuole might underlie the decreased accumulation of chloroquine by chloroquine-resistant parasites. In this study we have investigated the digestive vacuole pH of a chloroquine- sensitive and a chloroquine- resistant strain of P. falciparum, using a range of dextran-linked pH-sensitive fluorescent dyes. The estimated digestive vacuole pH varied with the concentration and pK(a) of the dye, ranging from similar to 3.7-6.5. However, at low dye concentrations the estimated digestive vacuole pH of both the chloroquine- resistant and chloroquine- sensitive strains converged in the range 4.5-4.9. The results suggest that there is no significant difference in digestive vacuole pH of chloroquine- sensitive and chloroquine- resistant parasites, and that digestive vacuole pH does not play a primary role in chloroquine resistance.