A question that we ask ourselves every summer, in vain: Why is it so difficult – if not impossible – to escape the ruthless detection of mosquitoes? Often accompanied by another question: Why do they bite me more than everyone else? Scientists and insect repellent manufacturers have known for some time that carbon dioxide (CO₂), exhaled during respiration, and octanol, a volatile compound found in sweat, form airways that mosquitoes use to lead them to their victims. What scientists didn’t know, but have now discovered, is that mosquitoes, unlike other creatures in the animal kingdom, have multiple smell and taste receptors in each of their thousands of olfactory neurons.

In 2004, researchers Richard Axel and Linda Buck won the Nobel Prize in Medicine for their discoveries relating to “olfactory receptors and the organization of the olfactory system”. A decade earlier, Axel and Buck had discovered that there were around 1,000 genes involved in the smell process, which are responsible for a similar number of olfactory receptors. Their work also showed that each olfactory sensory neuron expresses only one of these receptors – a phenomenon called the “one neuron – one receptor” rule – and that this information is then sent as an electrical signal to the olfactory bulb, the part of the mammalian brain that processes and interprets aromas. But according to Leslie Vosshall, head of the Neurogenetics and Behavior Laboratory at Rockefeller University in New York and a former postdoc in Axel’s lab, “all of Buck and Axel’s rules have been thrown in the trash by mosquitoes.” .

Vosshall leads a research program aimed at understanding the olfactory system of mosquitoes. Specifically, his work focuses on mosquito species Aedes aegypti, commonly known as the “dengue mosquito” for its role in spreading the virus that causes dengue fever. But Aedes aegypti is not only responsible for transmitting dengue – their bites can also introduce pathogens that cause yellow fever, chikungunya, Zika, and Mayaro virus disease. Understand how to block odor receptors from Aedes aegypti females – those that bite – could have major implications for global health and disease prevention.

The latest research results from Vosshall and colleagues, published in the scientific journal Cell, show that mosquitoes, like all other animals, have neurons with a single olfactory receptor. But they also found that Ah. Egyptian mosquitoes have many neurons co-expressing several receptor genes. “If you’re a human and you lose a single olfactory receptor, all of the neurons that express that receptor will lose the ability to smell that odor,” Vosshall says. “You have to work harder to knock out mosquitoes because getting rid of a single receptor has no effect. Any future attempt to control mosquitoes through repellents or anything else has to take into account how badly their attraction is unbreakable for us.

Once the mosquito genome was sequenced and the genes expressing the olfactory receptors identified, the researchers used various techniques to trace the genes and locate them in individual neurons. Using the modern gene-editing technique known as CRISPR, they were able to introduce different colored fluorescent proteins corresponding to different receptors, which then allowed them to see that many neurons had more than one receptor. asset. Vosshall’s team found that neurons stimulated by the human odorant octenol were also activated by other ammonia-derived chemicals, or amines, which also worked to attract mosquitoes.

“Surprisingly, the neurons for sensing humans via 1-octen-3-ol and amine receptors were not distinct populations,” says Boston University researcher and co-author Meg Younger. ‘study. In an email to EL PAÍS, Rockefeller University researcher Margo Herre, the study’s lead author, added, “Mosquitoes also use decanal and undecanal aldehydes. [volatile chemical compounds] and further research is needed to determine the exact composition of human odors and which of these odors mosquitoes are able to detect.

The big picture these results paint is that Ah. Egyptian have a double or triple redundancy system – that is, if they do not detect an odor, they switch to detecting a second or third odor. And if they detect them all, the signal is amplified. As Vosshall explains, “Mosquitoes have plan B after plan B after plan B. To me, the system is unbreakable.”

The results could have far-reaching implications. On the one hand, they could help explain why repeated attempts to control mosquitoes and limit their role in the spread of pathogens have all been more or less unsuccessful. As Younger explains, the woman Ah. Egyptian are hematophagous (which feed on blood) “because they need the proteins present in the blood to mature their eggs”. Mosquitoes’ eagerness and sophisticated ability to bite are the product of millions of years of evolution.

So far, attempts to block mosquito olfactory receptors by genetic modification have failed, perhaps because they all started from the commonly accepted idea – refuted by new findings – that a given gene expressed only one receptor for each type of neuron. This would also explain the relative, but not total, effectiveness of DEET, the repellent discovered by the US military in 1946 and which remains the main active ingredient in the vast majority of chemical insect repellents. Although its mechanism is not yet fully understood, N,N-diethyl-meta-toluamide (DEET) is thought to inhibit CO₂ or lactic acid receptors, but we now know that there are other odor receptors in the same neuron. The good part of the bad news is that researchers now understand that they need to focus their efforts on multiple receptors at once, not just one.

It remains to be seen whether this new finding also applies to other species of biting mosquitoes – Aedes albopictus, for example; other species of Anopheles, a genus of mosquitoes that transmit malaria; or Culexus mosquitoes, such as the common mosquito or the tiger mosquito, which tend to inflict only discomfort or itching except in rare cases. Christopher Potter, a neuroscientist at Johns Hopkins University School of Medicine, fears that might be the case. In 2019, his lab discovered that fruit flies (Drosophila melanogaster) also had double or triple expression of receptors in a single neuron, and in the spring of this year they published results indicating the same expression in a species of Anopheles mosquitoes.

Potter, who was not involved in the study, says “this redundancy may be common among insects.” Reflecting on the new findings, Potter explains how “the dogma before this was that an olfactory neuron would express only one type of olfactory receptor; that was the rule as far as we know. But, he says, “Dr. Vosshall’s work now suggests that a mosquito’s olfactory neurons may be much more adaptable, particularly towards the key odors it needs to detect to locate its hosts.