Map of malaria parasite's gene activity reveals new targets for drugs, vaccines

May 27 (UPI) -- New cellular maps of the malaria parasite have revealed the genetic transformations Plasmodium falciparum undergoes before infection.

The atlas, published Thursday in the journal Nature Communications, has already identified several potential targets for future drugs and vaccines.


Over the last 20 years, malaria-carrying mosquitoes have become increasingly resistant to pesticides, while the parasite itself has become increasingly unfazed by antimalarial drugs.

The lifecycle and development of P. falciparum, the unicellular protozoan parasite responsible for malaria, has been uniquely synced to optimize its ability to move from host to vector and back to host again.

P. falciparum begins its life in the midgut of a mosquito before migrating into the insect's saliva glands as it readies itself for the infection of a human host.

In 2019, this process played out at least 229 million times, resulting in 409,000 deaths -- both totals down slightly from the year before.

To identify potential new drug and vaccine candidates for malaria infections, researchers analyzed the gene activity associated with the parasite's different development stages.

Scientists isolated the parasite at different lifecycle stages and produced nearly 1,500 transcriptomes, maps of which genes are turned on and off at any given moment.


When turned on, certain genes within the parasite's genome direct the production of proteins that drive developmental changes and cause the protozoan to move from the mosquito's midgut to the insect's saliva glands.

Knowing which genes orchestrate this process -- and how -- can help scientists design drugs to disrupt the parasite's lifecycle and thwart infection.

"Being directly based on the human-infective parasite, our new data have clear implications for malaria control, which has an increasing focus on transmission blocking strategies both in terms of drugs that kill the parasite as it moves between stages and protective vaccines," study author Eliana Real said in a press release.

"Understanding how parasites behave transcriptionally within the mosquito vector provides a foundation from which new strategies will surely arise," said Real, a postdoctoral researcher and expert in sporozoite biology at Imperial College London.

In addition to identifying the genes that dictate development changes within the mosquito vector, researchers were able to isolate genetic changes related to the moment of infection.

Scientists did so by observing sporozoites, the cell form responsible for infection, as they were introduced to human skin cells.

By comparing the experimental data with transcriptomes of a related malaria parasite, Plasmodium berghei, which infects rodents, researchers were able to identify the genes that are shared by the two protozoans and those that are unique to the parasite responsible for human infections.


"This level of gene surveillance at the individual parasite level throughout its life cycle will provide an invaluable resource for researchers to discover previously unexplored elements of Plasmodium cell biology, comparative Plasmodium species biology and the development of control methods that target particular pathways or lay the foundations for improving vaccines," said co-author Farah Dahalan, research associate and expert on malaria parasite transmission at Imperial.

The authors of the latest paper have made all their transcriptomes and related data freely available online for other researchers to access.

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