In a new study, Vanderbilt University pharmacologist Dr. Jerod Denton, Ohio State University entomologist Dr. Peter Piermarini and colleagues reported on an experimental molecule that inhibits kidney function in mosquitoes and, thus, might provide a new way to control the deadliest pest.

The investigators aimed their inhibitor, named VU041, at the mosquito Anopheles gambiae, the leading vector for malaria, and Aedes aegypti, a mosquito that transmits Zika virus and other pathogens. The study appears in the journal Scientific Reports.

IMAGE: Vanderbilt scientists are part of a multi-institutional team studying an experimental molecule that inhibits kidney function in mosquitoes. Credit: Photo by James Gathany/CDC.

According to the announcement, over several decades of exposure, mosquitoes have evolved genetic resistance to various insecticides that attack their nervous system. The new study shows, for the first time, that inducing kidney failure — or, more correctly, Malpighian tubule failure — in mosquitoes can circumvent resistance to conventional insecticides.

"We're essentially preventing mosquitoes from producing urine after they take a blood meal," said Denton, associate professor of anesthesiology and pharmacology at Vanderbilt.

According to Denton, in taking a blood meal, mosquitoes can double or even triple their bodyweight.

Besides providing nutrients, blood meals carry toxic salts; the potassium chloride lurking in red blood cells, if not quickly voided, can depolarize cell membrane potentials and kill straight away.

"So, they've evolved a rapid diuretic process to very quickly separate the salt water from all the nutrients that they need for egg development. A lot of people don't realize that mosquitoes have kidneys, and when they take a blood meal from you, they also urinate on you almost simultaneously," Denton said. "What our compounds do is stop urine production, so (the  mosquitoes) swell up and can't volume regulate, and in some cases, they just pop."

Conventional mosquitocides cause the death of males and females at all stages of mosquito development and, in doing so, exert considerable selective pressure for the development of genetic resistance.

"By targeting blood-feeding female mosquitoes, we predict that there will be less selective pressure for the emergence of resistant mutations," Denton said.

The investigators showed VU041 to be effective when applied topically, which indicates that it potentially could be adapted as a sprayed insecticide. They also showed that it doesn't harm honeybees.

Arrangements are underway to test VU041 in a spray formulation. If that's successful, additional safety testing would be needed before deciding about commercial development, Denton said.