Researchers at Virginia Tech's College of Agriculture and Life Sciences have made a significant breakthrough in the fight against malaria. By preventing the malaria parasite from accessing essential fatty acids, the researchers found that the parasite's growth could be inhibited. This discovery could pave the way for new therapeutic treatments for the disease, which affected an estimated 249 million people in 2022.

Led by Michael Klemba, associate professor of biochemistry, the research team developed a screening method to identify and block the process by which the malaria parasite scavenges fatty acids instead of synthesizing them. The results, published in the journal Proceedings of the National Academy of Sciences, signify a promising new approach to combat malaria.

The malaria parasite relies on scavenging lysophospholipids, a type of host lipid, to fulfill its need for fatty acids. However, scientists have long been puzzled about how the parasite releases these fatty acids from the host lipids. The Virginia Tech team conducted experiments with infected red blood cells and identified chemicals that could halt the parasite's access to essential fatty acids.

Through their investigation, the researchers discovered the crucial role played by two enzymes in breaking down host lipids to release the necessary fatty acids. One enzyme functions outside the red blood cell, while the other operates within the parasite itself. By inhibiting the activity of both enzymes, either through genetic modifications or the use of drugs, the researchers observed that the parasites struggled to obtain the required fatty acids, thereby hampering their growth.

The findings suggest that the breakdown of lysophosphatidylcholine, a specific host lipid, is critical for the survival of the malaria parasite in the human body. Targeting these two enzymes could offer a novel strategy to combat the disease. Additionally, a previous study conducted in 2017 revealed that a drop in lysophosphatidic acid levels in the host triggers the conversion of the malaria parasite into a form that can be transmitted to mosquitoes.

According to Klemba, the presence of host lipids as a preferred source for fatty acids and the placement of one enzyme within the host cell are intriguing aspects of the malaria parasite's metabolic pathways. The researchers believe that this enzyme placement may be linked to the parasite's modification of the host red blood cell.

It is important to note that the research was carried out in vitro using a culture dish, and the potential toxicity of the compounds used to inhibit the two enzymes remains uncertain. However, Klemba suggests that some level of toxicity is expected, and efforts could be made to engineer compounds with reduced toxicity.

While further studies and clinical trials are needed, this significant breakthrough offers hope in the fight against malaria. By targeting the malaria parasite's ability to scavenge fatty acids, researchers at Virginia Tech have uncovered a potential avenue for the development of therapeutic treatments. With malaria remaining a global health concern, these findings could have a substantial impact on the lives of millions affected by the disease.

Reference:
Jiapeng Liu et al. Metabolism of host lysophosphatidylcholine in Plasmodium falciparum-infected erythrocytes, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2320262121