An international research team has shown for the first time that carbohydrates on the surface of malaria parasites play a critical role in malaria's ability to infect mosquito and human hosts.

The discovery also suggests steps that may improve the only malaria vaccine approved to protect people against Plasmodium falciparum malaria - the most deadly form of the disease.

The research, published in Nature Communications has shown that the malaria parasite 'tags' its proteins with carbohydrates in order to stabilize and transport them, and that this process was crucial to completing the parasite's lifecycle.

Authors identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP surface proteins.

Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice. These defects can be attributed to destabilization and incorrect trafficking of proteins bearing thrombospondin repeats (TSRs).

"We found that the parasite's ability to 'tag' key proteins with carbohydrates is important for two stages of the malaria lifecycle. It is critical for the the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people. Interfering with the parasite's ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito, and weakens the parasite to the point that it cannot survive in the host" senior author said.

Malaria infects more than 200 million people worldwide each year and kills around 650,000 people, predominantly pregnant women and children. Efforts to eradicate malaria require the development of new therapeutics, particularly an effective malaria vaccine.

https://www.nature.com/articles/s41467-017-00571-y