First published online May 8, 2008
Journal of Cell Science 121, 1003e (2008)
© The Company of Biologists Limited
Springing a chloroquine leak
Chloroquine is used extensively as an antimalarial treatment, but its efficacy has been limited by the emergence of chloroquine-resistant strains of Plasmodium falciparum, the parasite that causes malaria. Chloroquine is thought to kill the parasite by accumulating within its acidic digestive vacuole, and the intravacuolar accumulation of chloroquine is diminished in chloroquine-resistant (CQR) strains; however, the molecular basis of this decrease remains unclear. On page 1624, Kiaran Kirk and colleagues identify a possible pathway of chloroquine efflux from the vacuole of CQR parasites. The authors show that the leak of vacuolar H+ into the cytoplasm occurs at a faster rate in CQR than in chloroquine-sensitive (CQS) parasites. Moreover, in the presence of chloroquine the rate of H+ leakage increases dramatically in CQR parasites but not in CQS parasites. This chloroquine-induced H+ leak is inhibited by verapamil, which is known to increase chloroquine accumulation by CQR parasites. The authors propose, therefore, that chloroquine efflux from the vacuole occurs in tandem with H+ efflux in CQR – but not in CQS – parasite strains. These data shed light on the mechanism of chloroquine resistance in Plasmodium.
Related articles in JCS:
- A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites
- Adele M. Lehane, Rhys Hayward, Kevin J. Saliba, and Kiaran Kirk
JCS 2008 121: 1624-1632.
[Abstract]
[Full Text]
