Jammed traffic impedes parasite growth
- Department of Pharmaceutical Chemistry, University of Kiel, Gutenbergstrasse 76, D-24118 Kiel, Germany
Plasmodia are pathogenic protozoa that cause malaria in humans and other mammals, e.g., rodents. After infection through the bite of a mosquito, the parasites undergo a first developmental cycle in the liver and soon enter the blood stage by retreating into erythrocytes. During this phase, parasites proliferate rapidly and multiply up to 32-fold within 48 h. Synchronized bursting of red cells accompanied by high fever marks the end of one growth cycle. Within minutes, the released parasites invade new red cells to start another round. In a recent issue of PNAS, Liu et al. (1) demonstrate that the lack of a glycerol facilitator from the aquaporin (AQP) superfamily, i.e., AQP9, increases the resistance of infected mice: 2 weeks after infection all knockout mice were still alive, whereas 50% of the wild-type animals had died. AQPs constitute an ancient family of tetrameric channel proteins with individual pores in each monomer. In humans, 13 isoforms are known that facilitate transport of water and/or small, uncharged solutes across lipid membranes according to the prevailing osmotic or chemical gradients (2). The study by Liu et al. not only provides important insight into the interconnection of solute transport pathways between plasmodia and red cells, it may also prompt novel therapeutic approaches that target the parasite indirectly and thus have the potential to overcome the increasingly severe problem of resistance development.
Glycerol Uptake Across Three Consecutive Membranes
Inside red blood cells, three membranes shield the malaria parasite from the host's immune system, i.e., the red blood cell membrane, the parasitophorous vacuole membrane, which is derived from the red cell membrane and forms during invasion, and finally the parasite's own plasma membrane (see Fig. 1). Its sheltered lifestyle, however, makes the parasite dependent on the provision of nutrients and metabolic precursors by the host red cell. One property …
*E-mail: ebeitz{at}pharmazie.uni-kiel.de
