‘Kidney Punch’ Compound Could Stop Mosquitoes — Along with Their Resistance

WOOSTER, Ohio — You may someday hear less of that buzzing sound.

A team led by scientists from The Ohio State University and Vanderbilt University has taken the next step toward developing an improved, sustainable mosquito insecticide — one that won’t cause the biting, sometimes-disease-carrying pests to become resistant to it.

If successful, their work could one day help fight the spread of mosquito-borne illnesses such as Zika and malaria.

In an article published last fall in the journal Scientific Reports, Ohio State entomologists Peter Piermarini and Reed Johnson, Vanderbilt pharmacologist Jerod Denton, and colleagues reported several new findings about a mosquito-killing compound they’ve been studying, including that it seems safe for adult honey bees.

Piermarini and Johnson are faculty members in Ohio State’s College of Food, Agricultural, and Environmental Sciences. They’re based at the college’s research arm, the Ohio Agricultural Research and Development Center in Wooster in northeast Ohio.

Peter Piermarini (photo: Ken Chamberlain, CFAES)

Called VU041, the experimental compound targets a mosquito’s kidneys — or Malpighian tubules, to be exact — instead of its nervous system, as most current mosquito insecticides do. By doing that, Piermarini said, the new compound bypasses a mosquito’s mechanisms for developing resistance.

Possible new tool against diseases like Zika

Insecticide resistance is a “major challenge” in controlling mosquitoes, Piermarini said. It can hamstring efforts to control new mosquito-borne disease outbreaks when they occur, such as when Zika was detected last year in mosquitoes in parts of Miami, Florida — the first finding of the virus in mosquitoes on the U.S. mainland. Zika can cause birth defects in babies borne to infected mothers.

Resistance also can shrink what’s already a “very limited” arsenal of usable mosquito insecticides, Piermarini said.

“Most of the current mosquito insecticides target the nervous system, and in some cases, resistance to one of those insecticides leads to resistance to others,” he said. Because of that, he said, “We need to develop new insecticides that are toxic to mosquitoes via new mechanisms if we want to develop an effective chemical toolkit for controlling mosquitoes.”

Reed Johnson (photo: Ken Chamberlain, CFAES)

VU041 works by affecting certain potassium channels in the kidneys of adult mosquitoes, which shuts down the kidneys themselves. Potassium channels are types of proteins that regulate functions in cells.

The effect is problematic for female mosquitoes, because they, not the males, are the ones that feed on blood. Drinking all that liquid — equal to two to three times their body weight — makes them have to urinate.

Treated mosquitoes can’t go, may ‘pop’

But female mosquitoes treated with VU041 can’t go. They can’t excrete the salts and fluid that come from the blood they ingest. Result: They swell up and die. “In some cases,” Denton said in a Vanderbilt press release, “they just pop.”

For the study, the scientists looked specifically at VU041’s effects on the mosquitoes Aedes aegypti, the main transmitter of Zika, and Anopheles gambiae, a leading vector of malaria. They found, for example, that it:

• is toxic when applied to a mosquito’s cuticle, or outside surface;
• is toxic to mosquitoes resistant to current insecticides;
• doesn’t hurt adult honey bees, but further safety testing would be needed on honey bees’ other life stages and also on other insect species, including other beneficial pollinators.

“We included honey bee toxicity in the study because of concerns that existing insecticides used for mosquito and agricultural pest control are contributing to a decline in beneficial insects, such as honey bees and other pollinators,” Piermarini said. “We certainly don’t want to solve one problem, mosquitoes, by contributing to another one, honey bee decline.”

The team also determined that VU041 “moderately inhibits” a single potassium channel present in human heart tissue — a red flag in terms of its safety around people — but that a tweaked version called VU730 avoids the problem while still being effective against mosquitoes.

An ‘important step forward’

Taken together, the study’s findings suggest that VU041 or VU730 could serve as a chemical “scaffold” for creating a sprayed insecticide, Piermarini said.

“We’re still in the discovery stage of this research, so it could easily be five to 10 years away for a potential usable product,” he said. “But it’s an important step forward in our initial work that demonstrated that potassium channels in the kidneys of mosquitoes are valuable molecular targets for the development of new insecticides.”

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The Scientific Reports article is available online at nature.com/articles/srep36954. An Aug. 2, 2016, press release on Piermarini’s research is at go.osu.edu/BbAq.