What Mosquitoes Sniff
By Vivienne Baillie Gerritsen
In these parts of the world, it is hardly the time to talk of mosquitoes when the cold winter winds are still blowing. In other parts of the globe however, mosquitoes are out and about and causing millions of deaths yearly through their ability to transmit diseases, such as encephalitis, dengue, yellow fever and of course malaria. According to the World Health Organization, malaria alone is the cause of over two million deaths in Africa, one million of which are children under the age of five. A number of different mosquito species transmit malaria; these are the anopheline mosquitoes.
The female member of Anopheles gambiae is the mosquito which transmits malaria to humans. The question is why does it choose humans? The answer is it may well have to do with body odor. And where odor is involved, odorant receptors are also. It has recently been discovered that female A.gambiae do indeed have odorant receptors on their olfactive tissues which are specific for certain chemicals found in human sweat. And this is why they make a mosquito-line, so to speak, for certain humans. A greater understanding of the molecular processes, which underlie vector-host interaction, will help develop mosquito traps or repellents in the quest to beat malaria - or indeed other types of parasitic or viral diseases.
What causes malaria? It is neither a virus nor a bacteria but a plasmodium, a single-celled animal distantly related to an amoeba. Plasmodium falciparum and Plasmodium vivax are the two main culprits for causing malaria, the former being the more wicked of the two. When a mosquito sucks in human blood from a person suffering from malaria, it also sucks in the creatures causing the disease. The latter take advantage of this by reproducing inside the mosquito, waiting for the mosquito to dig its teeth into another host and seizing the opportunity to be released into the victim's blood thus causing a new infection. So what A.gambiae does - quite innocently in effect - is not only act as a taxi, which ships the disease from one host to another, but also as a cosy and quiet corner for the plasmodium to reproduce. And whilst A.gambiae acts as a taxi, human blood acts as a highway for the plasmodium.
Fig. 1 Anopheles gambiae at work
One way then to eradicate malaria altogether would be to empty all humans of their blood, wouldn't it? However, that is most obviously not an option. Interestingly, research on ways to fight off the disease has come round in a circle in the past 50 years. By the second half of the 20th century, entomologists were aware that it was the female mosquito which stung. A far cry from what was believed in the times of Julius Caesar. In those days, it had been noted that people who lived close to swamps and marshes were more susceptible to be struck down by malaria. Bereft of the knowledge of biology we possess today, the people assumed that the actual stench was the perpetrator of the disease. And this is where the word 'malaria' originates from: 'mal' meaning 'bad' and 'aria', air… And while we are flirting with the science of etymology, the word 'mosquito' is derived from the Spanish 'little fly'.
So, by the 1950s, scientists all over the world were imagining all sorts of experiments to understand not only why it was the female mosquitoes that were attracted but also how they were attracted. One of the experiments involved a human steel robot which was invariably warmed to body temperature, imbibed in human sweat or even made to exhale CO2. Research was blossoming until DDT made its appearance in the 1960s and was so effective as an insecticide that scientists' eagerness in understanding the vector-host interaction was somewhat dulled. However today, resistance to DDT coupled with second thoughts on the uncontrolled use of insecticides has flared an interest in alternative modes of fighting off mosquitoes.
The Anopheles gambiae genome has been completely sequenced. On it are found around 100 odorant receptor genes. These different odorant receptors are dispersed all over the mosquito's olfactive tissues. One of them, odorant receptor Or1 is found solely on female mosquito antennae and is particularly attracted to one of the 300 chemical compounds found in human sweat: 4-methylphenol. Or1 is a transmembrane G-protein coupled receptor, typically around 400 amino acids long. Its role, like all odorant receptors, is to bind its specific odorant. As a result, a number of downstream effector enzymes induce second messengers, which in turn stimulate odorant neurons. And the whiff of human sweat is transmitted to the brain thus giving the mosquito the drive to sting. What is more, not only does Or1 seek out 4-methylphenol for the mosquito's blood-feed but it also seems to have a role in turning off the process once the mosquito has had its fill. Indeed, once the insect is replete, the odorant receptor seems to be inhibited, perhaps following belly distension.
The existence of Or1 only in female mosquitoes - and hence its indirect role in its involvement in the transmission of malaria - as well as the discovery of its ligand should lead to interesting biotechnological applications in the quest for mosquito traps or indeed repellents. Substitute ligands could be synthesized which would trick the odorant receptors, and hence the mosquitoes, by disorienting them and leading them into a trap where they would be left to buzz aimlessly. Alternatively, ligands could be thought up which would inhibit the receptors and act as insect repellents. The discovery is promising. More research must be done to grasp in greater molecular detail the intricacies of vector-host interaction and then a cheap solution must be found to help fight off a disease which is one of the scourges of developing countries. Unfortunately, we cannot change how we smell - that is not the smell the mosquitoes are out for - but biotechnology could invent a way for mosquitoes to smell differently. And who would refuse a hot, humid summer night without unrelenting, whining mosquitoes?
Cross-references to Swiss-Prot
Q8WTE7: Anopheles gambiae (African malaria mosquito) odorant receptor Or1
1. Hallem E.A., Fox A.N., Zwiebel L.J., Carlson J.R.
Mosquito receptor for human-sweat odorant
2. Kanzok S.M., Zheng L.
The mosquito genome - a turning point?
Trends Parasitol. 19:329-331(2003)
3. Enserink M.
What mosquitoes want: secrets of host attraction
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