lecture
Biomolecular Sciences

Exploring the role of pipecolic acid in Plasmodium falciparumnnounced

Sonia Oren
December 26, 2024
15:00 - 16:00

Plasmodium falciparum (Pf) parasite is the major cause of malaria disease, resulting in more than 600,000 deaths annually. Patients with cerebral malaria, the most severe form of malaria, show elevated plasma L-pipecolic acid (PA) concentrations in their blood compared to those with mild malaria. However, the origin and function of PA in Pf infection remain mostly elusive. Here, using LC/MS targeted metabolomics we found that the malaria parasite, while growing inside its host human Red Blood Cell (RBC), secretes PA during a specific life stage, the trophozoite. We then demonstrated that pretreatment of the host naïve human RBCs with PA significantly enhances parasitic growth. To further investigate the effect of PA on its primary host, RBCs, we measured the biophysical alterations in the pretreated naïve RBCs using atomic force microscopy combined with machine learning.  Surprisingly, we found that PA modifies the mechanical properties of the host cell’s membrane, turning it significantly softer. Electron paramagnetic resonance data on liposomes suggest that PA’s mechanism may involve altering the lipid mobility. Overall, our findings reveal that the parasite secretes PA to prime its host RBCs for invasion by inducing mechanical changes in the stiffness of the host membrane. These results indicate that PA functions as an active secreted metabolite, facilitating Pf growth within its host cell.