* For medical professionals reading reference only


Summer, evening breeze, barbecue, beer, mosquito bun...
I believe that everyone who has been "popular" by mosquitoes will have such a moment of crazy. According to literature reports, a female mosquito bites multiple humans in its 3-6 weeks' life, and on average, a batch of new eggs will produce an extremely fast reproductive rate.
Of course, mosquitoes don’t treat everyone equally. I believe everyone has had this experience: if a group of people sit together, there will always be people who are bitten miserably, while some are unscathed. Studies have shown that some people are indeed more attractive to mosquitoes than others as mosquitoes [2]. However, the underlying mechanism behind "mosquito magnets" as a topic that attracts the public and scientific community is not yet clear.
Recently, the Rockefeller University team in the United States published a research article in the journal " cell ". By analyzing the skin odor of 64 individuals who are particularly attractive or unattractive to mosquitoes, found that the "mosquito magnet" human skin odor has higher levels of carboxylic acid . This research result not only provides ideas for the development of more effective mosquito repellents, but also is expected to provide new ways to curb the spread of dangerous insect arbitrary viruses [3].

researchers first used an olfactory detector to test the attraction of different individuals to mosquitoes. During the three-year study, the researchers conducted more than 2,330 behavioral tests.
In the preliminary experiment, the researchers randomly selected and compared the attractiveness of subjects No. 25, 28 and 33 to mosquitoes. found that No. 33 was significantly more attractive to mosquitoes than the other two experimental subjects, while No. 25 was slightly more attractive to mosquitoes than No. 28.
Considering the feasibility of the subjects conducting hundreds of trials over several months, researchers collected the odor of the subjects' forearm on the nylon sleeves and further compared the attractiveness of the 8 subjects to mosquitoes. It was found that there was a significant difference in the attractiveness of the 8 subjects. . 19 and 28 subjects' nylon sleeves were very low to mosquitoes, 25, 30, and 32 were moderately attractive, while 24, 31, and 33 were very attractive.

The attraction of different individuals to mosquitoes
In the comparison of the relative attraction of pairwise pairing, the researchers found that in almost every trial of , the number of mosquitoes attracted by No. 33 was significantly higher than other experimental subjects, and the gap was very large. In contrast, the attractiveness of No. 19 and No. 28 was significantly lower than that of several other subjects.
33 subjects were significantly more attractive to mosquitoes than other subjects, with an attractive score of 4 times that of the second attractive subjects and more than 100 times that of the two most unattractive subjects. In addition, the researchers also observed that this difference in attractiveness performed very stably within a few months.
So we can’t help but wonder, what magic does No. 33 have to do so to attract mosquitoes?

33 subjects have significantly higher attraction to mosquitoes than other subjects
mosquitoes mainly sense olfactory stimulation through two large multigene families: odor receptors (ORs) and ionization receptors (IRs) . Ors are mainly responsible for sensing odors such as esters, alcohols, ketones and aldehydes, while IRs mainly receive odor stimulation of carboxylic acids and amines [4].
Therefore, the researchers then constructed a series of mutants to explore the specific mechanism of mosquito preference for human odor. The results showed that mutations in odor receptor ORs co-receptors will not affect mosquito preferences for different individuals. Although ionizing receptor IRs co-receptor mutations generally reduce the attractiveness of human odor to mosquitoes to a certain extent, they will not affect mosquito preferences for different individuals.

ORs co-receptor and IRs co-receptor mutations did not affect mosquito preference for human individuals
Next, the researchers shifted the target to the odor differences on the nylon sleeve, trying to determine the compounds related to mosquito attraction on the nylon sleeve by using gas chromatography -quadrupole time-of-flight mass spectrometer (GC/QTOF-MS).Through unbiased feature detection and data filtering, the researchers found that there were 50 molecules in the samples of the two most attractive subjects (No. 33 and 31) of (No. 19 and 28), nine of which were linear fatty acids.
The researchers further extracted the signals of linear acids with a length of acyl on the subject's nylon sleeve with a length of between 3 and 20 carbons. Comparisons found that these compounds were low or absent in the unweared nylon sleeve and solvent control. Consistent with the aforementioned non-targeted analysis results, the researchers found that has a significantly enriched fatty acid in subjects with high attractiveness compared to subjects with low attractiveness, suggesting that individuals with high attractiveness to mosquitoes have higher carboxylic acid content in the skin odors.

has a high carboxylic acid content in individuals with high attractiveness to mosquitoes. To confirm the above findings, the researchers recruited 56 new subjects for verification study. It can be seen that different individuals have different attraction to mosquitoes. Of all 64 subjects tested throughout the study (8 in the preliminary cohort + 56 in the verification cohort), No. 28 was the least attractive, while No. 33 was the most attractive.
The researchers randomly selected 11 high-attractive subjects and 7 weak-attractive subjects from the cohort. A total of 18 subjects (4 in the initial cohort + 14 in the validation cohort) for GC/QTOF-MS metabolite analysis. After repeated experiments, the researchers concluded that the linear fatty acids pentadecanoic acid, heptadecanoic acid and nonanoic acid were significantly enriched in the samples of the high-attractive group.
Further researchers conducted targeted reanalysis of carboxylic acids containing 10-20 carbons in individual subjects and control samples. It was found that the overall carboxylic acid level in the subjects with lower attractiveness was significantly lower than that in subjects with higher attractiveness.

confirmed in the verification cohort that the carboxylic acid content is high in body skin odor.
In summary, the initial cohort and the verification cohort study results show that the different attraction of human individuals to mosquitoes are related to the richness of skin carboxylic acids, and high levels of skin carboxylic acid correspond to higher mosquito attraction.
A common explanation given by non-professionals is that differences in ABO blood types lead to differences in attraction to mosquitoes in different individuals, but the experimental data that explain this view is contradictory. Gladly, this article provides a new scientific explanation of the issue - "Mosquito Magnet" people with higher skin carboxylic acid content.
Edit Shendaotao
33, it's really amazing, the chosen one, so unlucky...

Reference:
[1] Ponlawat, A., and Harrington, L.C. (2005). Blood feeding patterns of Aedes aegypti and Aedes albopictus in Thailand. J. Med. Entomol. 42, 844–849.
[2] Bernier, U.R., Kline, D.L., Schreck, C.E., Yost, R.A., and Barnard, D.R. (2002).Chemical analysis of human skin emanations: comparison of volatiles from humans that different in attraction of Aedes aegypti (Diptera: Culicidae). J. Am.Mosq. Control Assoc. 18, 186–195.
[3] De Obaldia, Maria Elena et al. “Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels.” Cell, S0092-8674(22)01253-3. 17.
[4] Hallem, E.A., and Carlson, J.R. (2006). Coding of odors by a receptor repertoire. Cell 125, 143–160.


Author of this article丨Zhenzhenzhen
Editor丨Aboutiiyu