Unveiling the Protective Mechanisms of Pyruvate Kinase Deficiency against Malaria: Transforming Vulnerability into Resilience

Activity: Talk or presentationOral presentation


Malaria remains a global health challenge, and innovative strategies to control it are urgently needed. Exploring the interplay between the malaria parasite and host red blood cells (RBCs) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by reduced intracellular ATP levels and heightened 2,3-diphosphoglycerate (2,3-DPG)
concentration, has been associated with malaria resistance. Elevated 2,3-DPG levels, a specific mammalian metabolite, may hinder glycolysis, prompting us to hypothesise its potential contribution to PKD-mediated protection.
We investigated the impact of the extracellular supplementation of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. Results showed a hindrance of parasite growth, likely attributed to an impediment in parasite maturation, resulting in significantly less progeny from 2,3-DPG-treated parasites. Untargeted metabolomic analysis revealed that the
metabolic profile of treated infected cells became more similar to that of non-infected cells. To assess whether heightened 2,3-DPG affected RBC membrane properties and parasite invasion, we analysed alterations in membrane structure, cell morphology, and biomechanics using Atomic Force Microscopy. 2,3-DPG treatment induced mild modifications in RBC membranes compared to the profound influence exerted by the parasite on host cells. Mild modification of non-infected RBCs' height and stiffness did not impact the egress or invasion of parasite.
Since these findings strongly imply a direct influence of 2,3-DPG on the parasite, we analysed differential gene expression and the transcriptomic profile of schizogonic P. falciparum trophozoites, the most metabolically and transcriptionally active parasite asexual stage, from in vitro cultures submitted or not submitted to the action of 2,3-DPG, using Nanopore Sequencing Technology. 71 genes exhibited significant differential expression from the non-exposed parasites to 2,3-DPG and the parasite response seem to influence several cellular components and binding and channel activity molecular functions.
Period8 Dec 2023
Event titleCongress of Microbiology and Biotechnology 2023
Event typeConference
LocationCovilhã, PortugalShow on map
Degree of RecognitionInternational