Gene discovery uncovers source of resistance to malaria parasites in mosquitoes

Research lead

Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the Institut National de la Santé et de la Recherche Médicale (INSERM) in Strasbourg, France, have discovered variations in a single gene that affect mosquitoes’ ability to resist infection by the malaria parasite.

“Malaria parasites must spend part of their lives inside mosquitoes and another part inside humans, so by learning how mosquitoes resist malaria, we may find new tools for controlling its transmission to humans in endemic areas,” says Stephanie Blandin from INSERM.

The scientists worked with Anopheles gambiae mosquitoes, a major carrier of the parasite that causes the most severe form of human malaria in Africa, focusing on the mosquitoes’ resistance to the commonly used model organism Plasmodium berghei, a parasite that causes malaria in rodents.

When they compared the genomes of mosquitoes that can resist this infection with those of mosquitoes that cannot, they found the major difference lies in a single section of one chromosome. Of the roughly 975 genes contained in this section of DNA, one in particular, TEP1, appears to be important in determining a mosquito’s ability to resist infection.

TEP1 encodes a protein which is known to bind to and promote the killing of Plasmodium berghei malaria parasites in the mosquito’s midgut, and the scientists discovered the resistant mosquitoes had an allele of TEP1 that was different from those found in or susceptible strains.

To investigate whether this difference in alleles caused the variation in the mosquitoes’ resistance to malaria, the scientists developed a new technique, reciprocal allele-specific RNA interference, that can identify exactly which allele is behind a specific trait.

This showed that silencing different alleles produced mosquitoes with different degrees of resistance to malaria – meaning that an individual mosquito’s resistance to the malaria parasite depends largely on which form or forms of this one gene it carries.

Although this study focused on the parasite that causes malaria in rodents, there is evidence that this gene may also be involved in the mosquitoes’ immune response to human malaria.