Malaria Researchers’ Findings May Have Implications for Preventing Spread of Deadly Disease
ISB researchers and their collaborators are using systems biology approaches to learn how the malaria parasite is able to transfer to humans via the bite of an infected mosquito. The information they have uncovered may help identify new ways to prevent people from contracting the deadly disease.
Malaria is caused by Plasmodium parasites that are transmitted to humans through the bite of infected mosquitoes. Once inside the human host, the parasites invade the liver, multiply, and emerge to infect the blood, at which point they cause the clinical symptoms of malaria.
Mosquitoes that feed on infected blood are themselves infected and can spread the disease to others. In 2017, there were an estimated 219 million cases of malaria that resulted in 435,000 deaths, according to the WHO World Malaria Report. More than 60 percent of these deaths were children under five years of age.
“One of the reasons malaria remains such a formidable disease is the lack of an effective vaccine,” said ISB’s Dr. Kristian Swearingen, who studies the Plasmodium parasites.
The form of the malaria parasite that is transferred to humans – sporozoites – develop in cysts in the midgut of the mosquito and then travel to the insect’s salivary glands. There, the parasites lay in wait until the mosquito bites a human and injects parasite-laden saliva into the victim’s skin.
‘Promising targets’ for antimalarials
Swearingen, a senior research scientist in ISB’s Moritz Lab, used mass spectrometry to identify and compare the proteins present in sporozoites found in either mosquito midguts or salivary glands. Swearingen’s long-time collaborator, Professor Scott Lindner, and his team at Penn State quantified the messenger RNA (mRNA) in the same types of parasites.
The researchers found that, although parasites from midguts and salivary glands look identical under a microscope, there are certain genes that are only expressed in one stage or the other. For example, some of the proteins that are encoded by these genes are only used for infecting mosquito salivary glands, and are then switched off in favor of other genes that encode proteins the parasite will use for infecting humans.
“The proteins that are only made once the parasite is ready to infect a human represent promising targets for new antimalarial interventions, such as vaccines that train the immune system to recognize invading sporozoites,” Swearingen said.
One of the striking findings of the study arose from comparing the results of the two different technologies – transcriptomics (measuring which genes have been read into mRNA) and proteomics (measuring which proteins were actually translated from the mRNA). The research team found that, for certain genes, the ready-to-invade parasite makes an abundance of mRNA, but stores it away rather than letting it be translated into protein. Only when the parasite has invaded a human will it make the protein, which it then uses to infect the liver.
The proteins under this translational repression program also represent promising targets for antimalarials.
Swearingen and Lindner are co-first authors of a paper detailing these findings in the journal Nature Communications.