A step closer to understanding Food Vacuole Functionality in Malaria Parasite growth
Centre for Cellular and Molecular Platforms (C-CAMP)
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Malaria still poses a huge burden to global health with 247 million cases and 619,000 deaths reported in 2021 alone. Cerebral Malaria (CM) is a predominant cause of death in severe malaria infections caused by Plasmodium falciparum (Pf) with a mortality rate of 15-25%. However, pathology of CM is not fully understood as scope to study human cases with CM is limited.
Mass Spectrometry Facility at C-CAMP BLiSC India is glad to have supported a spearheading work from Dr Viswanathan Arun Nagaraj's Infectious Disease Biology Lab at DBT- Institute of Life Sciences, Bhubaneshwar on Plasmodium berghei (Pb), a rodent malaria parasite that has been an important model in studying disease pathology, particularly cerebral malaria. Arun's group has published a study titled
"Significance of Plasmodium berghei Amino Acid Transporter 1 (AAT1) in Food Vacuole Functionality and its Association with Cerebral Pathogenesis".
The study uncovers role of food vacuole transporters in malarial parasite growth and drug resistance, offering potential targets for malaria treatment and control.
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The food vacuole (FV) in malaria parasites plays a crucial role in the blood stage of development by digesting host hemoglobin (Hb) with FV proteases and detoxifying host heme into hemozoin (Hz). A crucial part of the aetiology of the disease is played by Hz, a malarial pathogen-associated molecular pattern (PAMP). Clinical and animal studies have linked Hz with disease pathogenesis and inflammatory immune responses in malaria. In this study, researchers examined the significance of Plasmodium berghei amino acid transporter 1 (AAT1) localized in the food vacuole. They found that targeted gene deletion of AAT1 led to a swollen food vacuole phenotype with a greater accumulation of host hemoglobin-derived peptides, still toxic to the organism, confirmed by LC-MS/MS & HPLC analyses for PbWT (Wild type) & PbAAT1KO (AAT1 Knockout) Parasite Food Vacuoles. The knockout parasites produced less hemozoin with thinner crystals and showed reduced sensitivity to antimalarials like chloroquine and amodiaquine. Mice infected with the knockout parasites were protected from cerebral malaria and displayed reduced inflammation and cerebral complications. Additionally, the knockout parasites exhibited a delay in male gametocyte exflagellation, affecting transmission. These findings demonstrate the importance of AAT1 in optimal food vacuole functionality and its association with malaria pathogenesis and gametocyte development. This study brings us step closer to understanding and combating malaria parasites by providing new insights about parasite AAT1.