Chloroquine resistance and the pH of the malaria parasite's digestive vacuole

The molecular mechanisms underlying chloroquine resistance in the malaria parasite are not well understood. Recent studies have focused attention on the role of the pH of the parasite's 'digestive vacuole', an internal acidic compartment in which ingested host cell proteins are degraded. In these studies, vacuolar pH was estimated from measurements of fluorescence from parasites stained with acridine orange. The validity of the method, and the conclusions drawn, have been challenged. Nevertheless, the correlation observed between acridine orange fluorescence and chloroquine resistance is intriguing and may well provide insights into the resistance mechanism. Whether vacuolar pH plays a role in chloroquine resistance remains an open question.