Global efforts to control malaria are severely compromised by the spread of resistance to the antimalarial drug chloroquine. The mechanism of resistance is not clear, but chloroquine is known to have its toxic effect in the parasite's digestive vacuole, and in resistant parasites, less of the drug accumulates in this vacuole. One proposal is that pH changes in the vacuole are responsible for chloroquine resistance. On , Kiaran Kirk and colleagues argue against this hypothesis, showing no significant difference between the pH of the digestive vacuoles of chloroquine-sensitive and resistant parasites. The authors preloaded erythrocytes with several dextran-linked pH-sensitive dyes and then infected them with chloroquine-sensitive or chloroquine-resistant parasites. The parasites endocytose the dye-loaded erythrocyte cytosol and deposit it into the digestive vacuole, thus allowing the authors to estimate its pH. Their findings indicate that the differences in chloroquine accumulation exhibited by sensitive and resistant parasites are not the result of differences in vacuole pH, and so the search for the origin of chloroquine resistance continues.
