Digesting Danger!

Behind the scenes of malaria infection, the parasite’s digestive machinery works nonstop to keep it alive. Central to this process is the digestive vacuole, the compartment where hemoglobin is broken down and where antimalarial drugs like chloroquine (Chloroquine? Where have I heard that before?) take effect. The chloroquine resistance transporter (CRT), embedded in the vacuole membrane, helps shape both parasite survival and drug response, yet its role across the parasite’s full life cycle remains unclear. To map when and where CRT is active, the Molecular Parasitology Group (Kai Matuschewski) used Plasmodium berghei parasites expressing a fluorescently tagged CRT. They found that CRT is strongly expressed during asexual blood stages and localizes to the hemozoin-rich digestive vacuole. Remarkably, CRT remains abundant in gametocytes and ookinetes, indicating that this organelle persists well into mosquito midgut development. Expression then shuts down during sporogony and early liver infection before reappearing in mature liver stages, likely priming the parasite for blood reinvasion. These observations reveal that the digestive vacuole — and CRT’s function within it — extends far beyond the erythrocytic cycle, offering fresh insights into parasite biology across hosts and vectors. You find more information in their Molecular and Biochemical Parasitology Article!

Abstract

Plasmodium parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we profiled the spatio-temporal expression of CRT during life cycle progression employing CRT-mCherry Plasmodium berghei parasites. We show that CRT is expressed during asexual blood stage growth and localizes to the hemozoin-containing digestive vacuole. The compartmentalized CRT-mCherry signal is also abundant in gametocytes and ookinetes, indicating that CRT continues to exert important functions in this digestive organelle up until mosquito midgut colonization. Expression is switched off during sporogony and early liver infection but CRT-mCherry is present again in mature liver stages, likely in preparation for blood infection. Together, visualization of the P. berghei digestive vacuole by endogenous tagging of PbCRT revealed expression of this transport protein and the presence of this cellular compartment beyond asexual propagation inside erythrocytes.