DEET blurs the sense of smell of the worms

summary

The round worm C. elegans is sensitive to the insect repelling effects of DEET. The discovery opens a new genetic toolbox that scientists can use to determine how DEET works.

<img alt = "Motion capture of DEET effects on worms" class = "caption" data-delta = "1" data-fid = "14535" data-media-element = "1" src = "https: / / www hhmi.org/sites/default/files/news/2018/hhmi_worm.gif "title =" A C. elegans the worm freezes when given a puff of DEET, before returning to action and moving normally. This video condenses 127 seconds. Credit: Emily Dennis and Leslie Vosshall "/>

The US Armed Forces have developed the DEET insect repellent more than half a century ago, but no one knows how the chemical prevents mosquitoes from biting. Howard Hughes Medical Institute (HHMI) investigator Leslie Vosshall's team is now approaching the solution.

In the small roundworms that live in the soil, the DEET contradicts smell, report Vosshall and his colleagues on September 26, 2018 in the review Nature. Worms, called Caenorhabditis elegans, have long been used in scientific research and there is an arsenal of genetic tools that scientists can now use to accurately probe the impact of DEET on insects. These extensive tools do not currently exist in mosquitoes, says Vosshall.

The work may one day direct researchers to more effective alternatives to DEET, she says. "You can not improve something if you do not know how it works."

The DEET is the gold standard for insect repellents, but it is far from perfect. The compound is oily, can damage clothing and must be reapplied at least every eight hours. According to Dr. Vosshall, a neurobiologist at Rockefeller University, it is not always possible to brag about DEET several times in areas where mosquitoes transmit life-threatening diseases.

"It has always been a dream in our field to find something that is not oily and does not need to be reapplied," she says.

<img alt = "" class = "caption" src = "http://www.hhmi.org/sites/default/files/News%20Images/vosshall_two_worms_793x396.jpg" style = "width: 700px; height: 350px; border : 0px "title =" Single C. elegans the worm stops (left) when it detects the DEET. Later, the worm begins to crawl (right). This image covers several images of a worm movie. Credit: Emily Dennis and Leslie Vosshall "/>

Scientists have developed three conflicting theories about how DEET interferes with insects. The chemical can confuse them, mask delicious smells or simply odorless. Previous Vosshall research suggests that DEET works more like a "confusing" than a repellent: the molecule somehow blurs the sense of smell of insects so they do not find their food. For mosquitoes looking for a blood meal, this means that they can not absorb human odors, such as odors and breathing.

DEET works well to deter mosquitoes – and it also upsets bees, ticks and leeches.

Vosshall graduate student Emily Dennis was fascinated by the effectiveness of DEET against animals separated by millions of years of evolution. A collaborator made him understand that the chemical seemed to even affect the behavior of C. elegans. So Dennis decided to test it.

First, she placed a drop of DEET in a plastic dish with C. elegans. The worms crawled as if the chemical was not even there.

Then Dennis added four smells of worms to the dish. Three seemed to be confusing the worms. Instead of heading for smells, the worms stopped or stopped on the spot, unable to move. Strangely, DEET did not confuse the worms' response to the fourth odor, a nauseating chemical called pyrazine. They quickly crawled to the smell.

"It tells us that some smells are affected by DEET and others do not," says Dennis. "DEET did not just paralyze the worms – something more interesting was happening."

<img alt = "DEET sensitive neuron" class = "caption" data-delta = "1" data-fid = "14537" data-media-element = "1" src = "https://www.hhmi.org /sites/default/files/news/2018/ewir74_str217gfp.png "style =" float: left; height: 521px; width: 700px; "title =" A DEET sensitive neuron that expresses the gene str-217 (green) plays a role in the confusing response of worms to insect repellent. Credit: Dennis et al./Nature 2018 "/ The Vosshall team mutated different genes into hundreds of individual worms to determine which genes were involved in the strange behavior.Then the researchers repeated the same odorous experiments, to see how specific genetic adjustments were affecting the response of worms to different flavors.

The researchers identified one gene and two neurons that seemed to be involved in the strange reaction of worms to DEET. The gene str-217 codes a protein in a pair of chemosensory neurons that helps the animal detect certain chemicals. The activation of these neurons caused a break of the worms, as they did with the DEET. And disabling the gene makes the worms resistant to the effects of DEET. The results suggest that DEET interferes with the neural circuits underlying the sense of smell of worms, eventually blurring their response to certain odors.

"The animal no longer recognizes that good things are good, and bad things are bad," says Vosshall.

The gene and neurons identified by his team are not found in mosquitoes. But Vosshall is confident that other genes that hide in the worm's genome might offer more clues about how DEET acts in biting insects. "What we learn will help us understand how DEET can reach and confuse a nervous system," she says. And that could help researchers develop a better repellent.

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Emily J. Dennis et al. "A natural variant and an artificial mutation in a GPCR promote resistance to DEET at C. elegans. " Nature. Posted online 26 September 2018. doi: 10.1038 / s41586-018-0546-8.