Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels

Background

Mosquito bites are not only unpleasant, but can pose severe health risks from viral infections including Zika or dengue fever. It is well known that some humans are more often the target of these insects than others (1). But what distinguishes these “mosquito magnets” from less preferred persons? To date, it is assumed that the differences are caused by variation in individual skin odors produced by humans, which are often linked to their unique skin microbiota (2). Interestingly, besides a heritable component, individuals can also become more attractive, for example following malaria parasite infection or beer consumption (3, 4). However, the specific chemical mechanism contributing to “mosquito attractiveness” is not known yet.

In their study, De Obaldia and colleagues clear up the myth of “sweet blood” by determining the differences in skin odor components between highly and weakly attractive humans. Furthermore, they shed light on the mosquitoes’ sensory pathways involved in the attraction to preferred individuals.

 

Main findings

• Mosquitoes strongly prefer some individuals over others

Initially, De Obaldia et al., compared the “attractiveness” of different individuals to female Aedes aegypti mosquitoes. They assessed mosquito preferences between the forearm skin odor collected on nylon sleeves of eight human probands using an adapted two-choice olfactometer (Fig. 1). By applying an attraction score system, they ranked the subjects from most to least attractive, with the most attractive subject being 100 times more attractive than the least attractive subjects. Of note, these preferences were stable over several months indicating that differences in skin odor remain consistent for long time periods.

 

Figure 1 (A) Top:  Illustration of the two-choice olfactometer setting: a mixture of air and CO₂ was blown over each stimulus to carry volatile odors to mosquitoes downwind. Mosquitoes flew upwind and those that reached one of the two traps in front of a stimulus were scored as “attracted”. Bottom: Picture of a model forearm on top of the stimulus box in the two-choice olfactometer. (B) Pairwise comparison of attractiveness of human-worn nylons to wildtype mosquitoes. Numbers on the x-axis indicate the subjects tested in the two-choice olfactometer assay (adapted from Fig. 1 De Obaldia et al., 2022, made available under a CC-BY 4.0 International license).

• Highly attractive humans have elevated levels of carboxylic acids

In the following, differences in the chemical composition of the skin odor between highly and weakly attractive individuals were assessed by gas chromatography/quadrupole time of flight-mass spectrometry (GC/QTOF-MS). This analysis revealed that highly attractive individuals produce increased levels of carboxylic acids. This class of organic acids typically contains a carboxyl group (C(=O)OH) attached to an R-group and includes among others fatty acids, amino acids and keto acids.

• Mosquitoes are equipped with a highly redundant and efficient sensory system

Mosquitoes detect olfactory cues with the help of odorant (ORs) and ionotropic receptors (IRs), which are both odor-gated ion channels. While ORs are mainly involved in sensing esters, alcohols and ketones, IRs bind carboxylic acids and amines (5). Mosquitoes lacking the OR co-receptor Orco were impaired in their ability to detect specific odors, but could still distinguished highly and weakly attractive individuals. Strikingly, mutating either of the IR co-receptors Ir8a, Ir25a, and Ir76b strongly affected the mosquitoes’ overall attraction to human scent but also maintained the ability to differentiate highly and weakly attractive people. This suggests the evolution of highly redundant sensory pathways which allow mosquitoes to detect attractive individuals even in the presence of severe genetic disruption of the olfactory system.

Why I chose this preprint

All of us might already have asked ourselves the question why some people are more attractive to mosquitoes than others. Although olfactory cues in human skin odor seem to play a major role, not much is known about the specific chemical mechanism. In their study De Obaldia et al. identify carboxylic acids as a class of compounds that are very likely to contribute to the “attractiveness” of an individual. Furthermore, their investigation of the sensory pathways involved allows us to perceive the redundancy and high effectivity of the mosquitoes’ olfactory system, which have evolved in a fascinating evolutionary process. Ultimately, this knowledge can help to develop more effective strategies to protect “mosquito magnets” from mosquito bites and prevent the spread of diseases caused by these insects.

Questions

1. As pointed out, due to limited sample size, human subjects were not further divided into subgroups regarding demographic factors such as sex and age, or other factors like dietary habits. Nevertheless, did you notice any striking features distinguishing highly from weakly attractive individuals, for example were there obvious gender or age differences?
2. Given that microbiota play a key role in the production of skin odor, are you planning to map the skin microbiome of highly and weakly attractive individuals to identify strains associated with increased carboxylic acid production?

References

1. Qiu, Y. T., et al. “Interindividual variation in the attractiveness of human odours to the malaria mosquito Anopheles gambiae ss.” Medical and veterinary entomology3 (2006): 280-287.
2. Verhulst, Niels O., et al. “Composition of human skin microbiota affects attractiveness to malaria mosquitoes.” PloS one12 (2011): e28991.
3. De Moraes, Consuelo M., et al. “Malaria-induced changes in host odors enhance mosquito attraction.” Proceedings of the National Academy of Sciences30 (2014): 11079-11084.
4. Lefèvre, Thierry, et al. “Beer consumption increases human attractiveness to malaria mosquitoes.” PloS one3 (2010): e9546.
5. Benton, Richard, et al. “Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila.” Cell 136.1 (2009): 149-162.

Tags: mosquito, sensory system, skin odor

doi: https://doi.org/10.1242/prelights.31274

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