Parasite That Causes Malaria Extracts Fatty Acids From Human Hosts for Growth

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Malaria has a large global burden, affecting hundreds of millions of people each year.

Malaria-causing parasites were found to use 2 enzymes to extract fatty acids from host cells, allowing the parasite to grow and reproduce in host red blood cells, according to investigators with the Virginia Tech College of Agriculture and Life Sciences who published their findingsin Proceedings of the National Academy of Sciences. The parasite could not grow when investigators inhibited these enzymes, bringing a possible new mechanism to fight malaria.1

Credit: xyz+ - stock.adobe.com

Credit: xyz+ - stock.adobe.com

“The key to this breakthrough is that we were able to develop a screening method for the malaria parasite and block this process,” said lead investigator Michael Klemba, associate professor of biochemistry, in the press release. “While very much in its infancy, the results could open the door to a new way to fight malaria.”

Unlike humans, the parasite that causes malaria, Plasmodium falciparum, cannot create its own fatty acids. Since it cannot create fatty acids—an important nutrient for survival and growth—Plasmodium falciparum enters human red blood cells and breaks down lysophospholipid, a type of host lipid, instead.

Previous studies suggest that human host lipids are the parasites’ primary choice of lipid source, but investigators did not understand the metabolic pathways allowing these parasites to get fatty acids from the lipids.

“If we could show that that these metabolic pathways were useful, then that would be an important contribution to the field,” Klemba said in the press release.

During this study, Virginia Tech investigators experimented on infected red blood cells to understand how parasites accessed the fatty acids for growth and reproduction in red blood cells. The team identified 2 enzymes (XL2 and XLH4) that could promote parasite growth, 1 of which works inside the parasite, the other inside the red blood cell.

When investigators removed these enzymes (via changing the parasite’s genes or drugs), the parasite could not successfully extract fatty acids from the lysophospholipid—thus, it could not effectively grow in human blood. The study was limited by its in vitro design, which limits understanding of the toxicity associated with enzyme inhibitors, but the study authors noted thatthe findings remain fruitful in the fight against malaria.

Malaria is a common and fatal disease caused by a parasite that is transmitted to humans via mosquito bites. Mild symptoms of malaria include fever, chills, and headache, and severe symptoms include fatigue, seizures, confusion, and difficulty breathing.2

Nearly all estimated cases of malaria (249 million in 2022) occur in Africa. Despite the disease being both preventable and curable, 608,000 people died from it globally in 2022, according to estimates, with 95% of deaths occurring in Africa and approximately 80% of the region’s deaths occurring in children aged younger than 5, highlighting a significant and inequitable disease burden.

REFERENCES

1. Virginia Tech researchers discover that blocking an essential nutrient inhibits malaria parasite growth. Virginia Tech. News Release. February 13, 2024. February 15, 2024. https://www.eurekalert.org/news-releases/1034333

2. Malaria. World Health Organization. News Release. December 4, 2023. Accessed on February 16, 2024. https://www.who.int/news-room/fact-sheets/detail/malaria#:~:text=Malaria%20is%20a%20life%2Dthreatening,be%20mild%20or%20life%2Dthreatening.

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