G6PD deficiency and the exportome of plasmodium falciparum FCB-2: A comparative analysis utilizing one-dimensional blue-native electrophoresis and timstof mass spectrometry.

Plasmodium falciparum, the etiological agent of severe malaria in humans, remodels the surface of infected erythrocytes to evade host immune defenses and ensure its survival. During its intraerythrocytic development, P. falciparum modifies the composition of protein complexes within the host cell membrane and cytoskeleton by exporting parasitic proteins to the surface of the infected erythrocyte. However, there is limited understanding of its behavior in cells harboring protective polymorphisms against severe malaria, such as those associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency, where reduced adhesion and early phagocytosis have been observed due to oxidative damage to the surface proteins of parasitized erythrocytes. Nonetheless, the impact of G6PD deficiency on the exportome proteins of P. falciparum in infected erythrocytes remains to be elucidated. In this in vitro study, we conducted a comparative analysis of the P. falciparum FCB-2 exportome in G6PD-deficient versus normal human red blood cells. Two membrane protein conglomerates were isolated at the ring, trophozoite, and schizont stages using Blue-Native electrophoresis, followed by in-gel digestion and LC-MS-tims-TOF analysis. The analysis revealed a significant decrease in the number of P. falciparum proteins identified in all asexual stages for both protein conglomerates on the surface of infected G6PD-deficient erythrocytes. A decrease in the number of effector, adhesion, trafficking, and signaling proteins that reinforce the protective mechanisms previously described was observed. These findings provide new insights into the pathways for understanding the molecular events that support G6PD's protective mechanisms against malaria.