The Wellcome Trust Lecture: Mechanisms of molecular trafficking in malaria

Abstract

SUMMARYThe asexual stages ofPlasmodiumliving within the erythrocyte result in growth-related changes in the permeability properties of the red cell for substances such as glucose, amino acids, purine nucleosides, sodium, potassium, calcium, zinc, iron and several antimalarial drugs such as chloroquine, amodiaquine and mefloquine. In most cases such changes do not appear to be due to a modification in the affinity or specificity of red cell transporters; indeed, for most substances the membrane-associated transporters are either unaffected or are partially inactivated. In malaria-infected erythrocytes, where a striking increase in influx has been observed, it has been attributed to the insertion of parasite-encoded transporters into the red cell membrane or the formation of aqueous leaks and/or pores. Leak formation, in the vast majority of cases, does not appear to be dependent on the insertion of plasmodial proteins into the red cell membrane. However, since the data presently available are less than satisfactory for discriminating amongst the various possible transport mechanisms future studies will require painstaking efforts and carefully controlled conditions to discriminate amongst the various transport systems which are operational in the malaria-infected red cell and the parasite.

Enhancement of Splenic Glucose Metabolism During Acute Malarial Infection: Correlation of Findings of FDG-Pet Imaging With Pathological Changes in a Primate Model of Severe Human Malaria

“…It is known that host glucose is the main energy source for asexual stages of P. falciparum and that the more mature form of the parasite consumes up to 70 to 80 times the amount of glucose required by uninfected erythrocytes in vitro. 31,32 Interestingly, in the current study, blood glucose level was significantly lower at second PET scan, whereas splenic FDG level was markedly increased in all infected monkeys. Histo- logic examination of infected tissue revealed massive congestion by numerous PRBCs in the red pulp.…”

The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro

“…Another factor which might be influential in determining the susceptibility of the parasites to NO and iron chelators is the permeability of the membrane of the infected erythrocyte. This increases from ring stage to schizont stage facilitating the transport of nutrients and waste products in and out of the red cell, aided by a tubovesicular network extending from the parasitophorous vacuole into the red blood cell ( Sherman 1988, Deitsch & Wellems 1996). At the same time, there are changes to the phospholipid organization of the red cell membrane, leading to altered red cell membrane fluidity ( Sherman & Greenan 1984, Schwart et al .…”

Effects of cinnamic acid derivatives on in vitro growth of Plasmodium falciparum and on the permeability of the membrane of malaria-infected erythrocytes

“…It is clear that the total lactate transport capacity of human erythrocytes cannot sustain the increased lactate production of infected cells (6,13). An (6,13), and glycine (27). That of the malaria-infected cell displays new permeability pathways accessible to these and other solutes (10), including sorbitol (10 [469][470][471][472][473][474][475][476]1991).…”