It's no secret that mosquitoes find some humans more tasty than others or that they dislike certain repellents.
Scientists don't know why, but some researchers at the Johns Hopkins University may be closer to solving those mysteries about the world's deadliest animal.
A Hopkins team led by neuroscience professor Christopher Potter genetically modified mosquitoes so that their nerve cells for smell would glow green, allowing them to see how the little buggers smell and taste in greater detail.
They discovered that smelling nerves in a mosquito's proboscis, the elongated mouthpart used to suck blood, connect to a part of the brain related to taste, suggesting that mosquitoes are experiencing different flavors when they bite humans.
The findings, published in Nature Communications in October, could unlock why some humans get bitten more by mosquitoes than others, potentially leading to the development of more powerful repellents or other solutions. The results of the research could have significant implications for the hundreds of thousands of people worldwide who die from malaria each year, and those at risk for other mosquito-borne illnesses such as Zika.
"More humans are killed by mosquitoes than by humans, so it's pretty relevant for human health," said Potter, who is part of the Johns Hopkins Malaria Research Institute. "Mosquitoes, because they can carry diseases, they're always going to be a problem for humans. And so the better we can understand them and keep them from biting us, the better we can keep ourselves healthy around the world."
Potter previously worked with fruit flies to refine the technique for making certain insect cells glow green. Mosquitoes are much more difficult to genetically modify than fruit flies, he said, but he was able to adapt the strategy. The team made the insects' olfactory, or smell, nerve cells glow green under fluorescent light by adding genes from the Neurospora fungus, which comes from bread mold, and from the Aequorea jellyfish.
The team modified the Anopheles gambiae mosquito, a species known for transmitting malaria. Only female mosquitoes bite humans because they need a blood meal to incubate eggs.
There were about 214 million malaria cases and an estimated 438,000 malaria deaths in 2015 — mostly in Africa, according to the World Health Organization. Mosquitoes also transmit diseases such as dengue and Zika, which causes devastating birth defects.
Thousands of the mosquitoes in adult and larvae stages live in a small, sealed room on the Johns Hopkins campus. The temperature is kept at a balmy 80 degrees with 70 percent humidity. To study the mosquitoes, the team puts them on ice for several minutes, which knocks them out temporarily.
The researchers found that smell nerves in the proboscis were linked via a nerve connection known as an axon to a region in the brain thought to be only involved in taste. In humans, smell and taste senses mix to give a sense of flavor, which is why food tastes blander when a person's nose is stuffed up from a cold. Smell and taste mixing to create flavor also may be happening in mosquitoes, Potter said.
"When they're actually feeding on us, this particular nose is very close to our skin, and so they're tasting and smelling us at the same time, they're flavoring us," Potter said. "And that might be how they decide who they like to bite and who they don't like to bite."
Anandasankar Ray, an associate professor at the University of California, Riverside who conducts similar research, compared the finding to discovering that the tongue of a human was sensing odors instead of tastes.
"Those trying to disrupt insect behavior, they will be able to study this class of olfactory neurons in a different way," he said. "They can ask, why is it that the tongue of the mosquito is sensing odors?"
Jeff Riffell, an associate biology professor at the University of Washington, said most of the mosquitoes' senses are geared toward finding blood-bearing hosts, whether human or another animal.
"It's fascinating because it was really not what you predict, and it suggests that taste and smell is coupled in the mosquito, perhaps to form their host-seeking behaviors," Riffell said.
He predicted that in the next 10 years, scientists would be able to develop a variety of methods to keep mosquitoes from biting humans.
"With this kind of tool kit and understanding, what Chris and others can now do is target and genetically modify the mosquitoes to modify their behavior," he said. "I think you're going to be seeing a lot of these genetically modified mosquitoes."
Some humans are bitten more frequently by mosquitoes, indicating that there may be something about them that smells or tastes better to the insects, Potter said. His team at Hopkins hopes to study next why repellents such as DEET work, potentially leading to the development of more effective and safer repellents.
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Learning more about how mosquitoes experience smells, tastes and flavor also could lead to products that attract mosquitoes away from humans. Because mosquitoes use their sense of smell to find mates and determine good places to lay eggs, scientists could develop ways to stop the mosquitoes from doing those two activities.
"There's lots of different places where we could manipulate their behavior just by using their sense of smell," Potter said.
If mosquitoes stopped biting humans, they would turn to other animals to feed. But the most common mosquito-borne diseases, like the malaria parasite, do not survive well in other animals, so the disease eventually could die out, Potter said.
He said it was unlikely that birds, fish or other insects that eat a genetically modified mosquito would suffer any harm. The mosquitoes that carry dangerous diseases also play a minor role in the ecosystem as a source of food, and if they were eliminated completely, there would likely be little impact, he said.
Potter, who has been working with the mosquitoes for about two years, said he hopes to develop new repellents in the next couple of years.
"Mosquitoes have been a problem for thousands and thousands of years," Potter said. "The ultimate goal is to stop mosquitoes from biting us and stop the spread of diseases."