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Novel insecticide blocks mosquitoes’ ability to urinate

Mosquitoes spread many diseases and cause millions of deaths each year around the world. Unfortunately, they are developing resistance to many insecticides. CDC/James Gathany

A bite from a mosquito can be much more than just an itchy annoyance. Mosquitoes carry and spread several serious diseases, including dengue, malaria, chikungunya, yellow fever, and Zika. Globally, mosquitoes cause millions of deaths each year.

Several insecticides are currently available to control mosquitoes. These target their nervous system. Unfortunately, mosquitoes are developing resistance to these compounds.

When mosquitoes take in a blood meal, they can double or triple their body weight. The blood provides nutrients, but also contains an excess of salt, such as potassium chloride. Mosquitoes have kidneys (Malpighian tubules) that excrete excess salt and water from their body fluid. As they take in a blood meal, they urinate to dispose of the waste products.

A research team led by Drs. Jerod S. Denton of Vanderbilt University Medical Center, Peter M. Piermarini of Ohio State University, and Corey Hopkins of the University of Nebraska Medical Center set out to develop a new class of insecticides that target the mosquito kidney. Their research was supported by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published online on November 16, 2016, in Scientific Reports.

The scientists screened about 26,000 compounds for their ability to inhibit a specific potassium channel, called Kir1, that’s involved in urine production. They identified 121 compounds.

The team found that one very potent compound known as VU041 rapidly blocked Kir1 channel activity. It was specific to mosquitoes; it didn’t affect any mammalian potassium channels tested.

Topical application of VU041 was toxic to both insecticide-susceptible and insecticide-resistant strains of female mosquitoes, including both Anopheles gambiae (malaria carrier) and Aedes aegypti (dengue, yellow fever, and Zika virus carrier). Topically applied VU041 wasn’t toxic to adult honeybees.

The team monitored mosquitoes to assess kidney function. When untreated mosquitoes consumed a blood meal, their abdominal diameter immediately doubled, and then decreased over the next 24 hours. In contrast, the abdominal diameters of mosquitoes treated with VU041 increased but didn’t decrease, suggesting that kidney function was impaired. The scientists also found that VU041 reduced egg laying after blood feeding.

“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. What our compounds do is stop urine production, so they swell up and can’t volume regulate, and in some cases they just pop,” Denton says.

Further research will be needed to determine the agent’s precise mechanisms of toxicity and to assess its impact on humans, as well as on honeybee colonies and other beneficial insects.

—by Carol Torgan, Ph.D.