falciparum-infected red blood cells Excess hemoglobin digestion and the osmotic stability of Plasmodium

During their asexual reproduction cycle (~ 48 h) in human red cells Plasmodium falciparum parasites consume most of the host cell hemoglobin, far more than they require for protein biosynthesis. They also induce a large increase in the permeability of the host cell plasma membrane to allow for an increased traffic of nutrients and waste products. Why do the parasites digest hemoglobin in such excess? And how can infected red cells retain their integrity for the duration of the asexual cycle when comparably permeabilized uninfected cells hemolyse earlier? To address these questions we encoded the multiplicity of factors known to influence host cell volume in a mathematical model of the homeostasis of a parasitised red cell. The predicted volume changes were subjected to thorough experimental tests by monitoring the stage-related changes in the osmotic fragility of infected red cell populations. The results supported the model predictions of biphasic volume changes comprising transient shrinkage of infected cells with young trophozoites followed by continuous volume increase to about 10 % below the critical hemolytic volume of ~ 150 fL by the end of the asexual cycle. Analysis of these results and of additional model predictions demonstrated that the osmotic stability of infected red cells can be preserved only by a large reduction in impermeant solute concentration within the host cell compartment. Thus, excess hemoglobin consumption represents an essential evolutionary strategy to prevent the premature hemolysis of the highly permeabilized infected red cell. For personal use only. by guest on June 10, 2013. bloodjournal.hematologylibrary.org From