Depending on where you live, the buzz of a nearby mosquito can be a nuisance, or it can be deadly. Worldwide, more than 500 million people suffer from diseases transmitted by the blood-feeding insects, including malaria, Dengue Fever, Zika, and West Nile, and nearly a million deaths are attributed to mosquito-borne illnesses each year.
Researchers at the University of Arizona have discovered a protein in mosquitos that is critical to the process of producing viable eggs and could pave the way for “mosquito birth control.” When researchers selectively blocked the activity of the protein — which they named Eggshell Organizing Factor 1, or EOF-1 — in female mosquitoes, the mosquitos laid eggs with defective egg shells, leading to the death of the embryos inside.
In the report, published in the open access journal PLoS Biologyon Jan. 8, the team showed that EOF-1 exists only in mosquitoes. Therefore, any drug developed to render the protein dysfunctional would only affect mosquitoes and no other organisms.
The team, led by Jun Isoe, a research scientist in the lab of Roger Miesfeld, a UA Distinguished Professor and head of the Department of Chemistry and Biochemistry, is hopeful the approach might offer a way to interrupt mosquito egg formation and reduce mosquito populations in areas of human disease transmission without harming beneficial insects such as honey bees.
“We specifically looked for genes that were unique to mosquitoes and then tested for their functional role in eggshell synthesis,” Isoe says. “We think there are other discoveries to be made using this same species-directed approach.”
Isoe first used a bioinformatics approach to search for and identify genes that are unique to mosquitoes. None of those genes were previously known with regard to their function. The research team then created small RNA molecules that specifically inhibit each of the proteins the genes code for. Known as RNA interference, or RNAi, the technique works by suppressing messenger RNA molecules that serve as blueprints for proteins.
Focusing on the previously identified candidate genes one at a time, the RNAi molecules were injected into female mosquitoes right before a blood meal. Only female mosquitoes bite because they need a blood meal to produce eggs; the males visit flowers to drink nectar. Once a female mosquito has had a blood meal, her follicles develop and it takes three days to lay eggs.
Each individual mosquito was screened for viable offspring. Out of the 40 mosquito-specific genes the team tested, only one, the EOF-1 gene, was found to disrupt eggshell formation and result in the death of the mosquito embryo.
A female mosquito needs a second blood meal in order to produce next the batch of fertilized eggs. Usually, the effects of RNAi injection last only through one egg-laying cycle, but in the case of EOF-1, the researchers were surprised to find that treated females could no longer produce viable eggs for the rest of their two- to three-week life span, even after three consecutive blood meals.
“This lasting effect makes the EOF-1 protein a very attractive target for drugs,” Miesfeld says.