Description
It is urgent to find new efficacious tools against malaria. Mechanisms of parasite interaction with the host red blood cell (RBC) may provide targets for novel host-directed antimalarial approaches. Pyruvate kinase deficiency (PKD) has been associated with resistance to malaria. PKD-cells present a decrease in ATP and an increase in 2,3-diphosphoglycerate (2,3-DPG) concentration. High levels of this mammalian metabolite have an inhibitory effect on glycolysis and we hypothesized that its accumulation may be involved in the protection provided by PKD. We examined the effect of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. Results showed impaired parasite growth, with significantly lower progeny emerging from parasites that were treated with 2,3-DPG. Furthermore, the metabolic profile of infected cells became closer to that of non-infected RBCs (niRBCs). To evaluate if increased 2,3-DPG also affected the RBC membrane and parasite invasion, we explored modifications of RBC membrane, morphology and biomechanical properties. Cells infected with P. falciparum were more rigid and showed altered morphology, with a decrease on their area:volume ratio. The extracellular addition of 2,3-DPG slightly affected niRBCs height and stiffness, making the latter more similar to that of infected cells. Moreover, the membrane surface charge was more negative in treated RBCs than in untreated ones. Our results indicate that treatment with 2,3-DPG has a mild effect on RBC membranes compared to the parasite’s effect on the host cell. As an endogenous host metabolite, 2,3-DPG may, in the future, originate a new antimalarial tool with few adverse effects on noninfected cells.Funding: PTDC_BIA-CEL_28456_2017 and GHTM—UID/04413/2020
| Period | 20 Apr 2023 |
|---|---|
| Event title | 6º Congresso Nacional de Medicina Tropical |
| Event type | Conference |
| Location | Lisboa, PortugalShow on map |
| Degree of Recognition | National |