The malaria parasite Plasmodium falciparum contains an organelle called an apicoplast. It’s akin to a chloroplast found in plants, but without the ability to photosynthesize.
It’s believed that the ancient ancestor of the malaria parasite at some point ate a cyanobacteria, just as plants in the ancient world ate what became the chloroplast, explained pediatrician and molecular microbiologist Audrey R. Odom, MD, PhD, of Washington University School of Medicine in St. Louis. “Although the parasite has lost photosynthesis, it still has all of these plant-like metabolic pathways,” she said. “Because plants use these metabolic pathways to make a class of compounds called terpenes, which give off tell-tale odors, we thought there might be terpenes in the malaria parasite.”
Much to Odom’s delight, that’s exactly what she found. In a study in mBio this week, Odom and colleagues describe how terpenes produced by P. falciparum release odors that attract mosquitoes. The work suggests that humans or animals infected with malaria are more likely to be bitten by a mosquito, or more likely to be bitten more than once.
The work could lead to new diagnostic tests for malaria, Odom said: “We hope these kinds of parasite-produced compounds are the sort of thing that you might be able to find in the breath or sweat of children with malaria. We have studies ongoing to see if we can detect these compounds in children with malaria, because obviously a breathalyzer test would be a lot nicer than the blood-based tests that are currently used.”
The work also holds implications for malaria control, she said: “Understanding the molecular basis of mosquito attraction and host choice is important for figuring out how you might prevent people from getting bitten in the first place.”
She and her colleagues had been studying malaria parasite cultures in human red blood cells, grown in airtight bags. For this study, they sampled the gas on top of the liquid culture in the bags and used gas chromatography-mass spectrometry to analyze the chemical components of the gas. They compared gas samples from bags containing malaria-infected red blood cells to gas samples taken from bags containing uninfected red blood cells and from empty bags.
The investigators found that, like plants, P. falciparum uses a chemical pathway called MEP to produce terpenes. They found four compounds specific to the parasite-infected samples, including two terpenes. Each malaria-infected sample studied had at least one type of terpene such as limonene (a substance that makes lemons smell like lemons) and pinanediol (related to the substance that makes pine trees smell like pine trees). Terpenes were not found in gas samples from bags of uninfected cells or from empty bags.
Additional tests determined that terpenes emitted by malaria-infected red blood cells arose from the MEP pathway, and that the type of mosquitoes that transmit malaria have the ability to detect these terpenes.
“Together, our studies provide evidence that malaria parasites produce specific compounds that attract mosquitoes, and that the mosquitoes that transmit malaria contain the cellular machinery necessary for detecting and responding to these compounds,” Odom said.
Odom’s laboratory is interested in teasing out the proteins and enzymes in the parasite, as well as the biosynthetic machinery that makes them, to assess biological function. “We’re also interested in taking forward the biomarker angle and trying to identify whether or not these compounds are actually present in natural malaria infection.”
Researchers at Yale University contributed to the work.