My personal opinion is: If such kind of mosquito studies could goes another way, discovering the very plants which could easily plant surrounding our house or environments in order to reduce mosquitoes or bad insects, I think it will be helpful in some wild area, just like Africa.
But there is also a problem: What if this could makes mosquitoes generate drug resistance?
Targeting a Dual Detector of Skin and CO2 to Modify Mosquito Host Seeking
Cell, Volume 155, Issue 6, 1365-1379, 5 December 2013
Copyright © 2013 Elsevier Inc. All rights reserved.
- Mosquito CO2 neurons (cpA) detect human skin odor and are important for attraction
- In silico screen of >440k chemicals finds excellent agonists and antagonists of cpA
- Blocking cpA activity abolishes attraction behavior toward human skin odor and CO2
- Agonists that lure mosquitoes to traps represent safe affordable control
Female mosquitoes that transmit deadly diseases locate human hosts by detecting exhaled CO2 and skin odor. The identities of olfactory neurons and receptors required for attraction to skin odor remain a mystery. Here, we show that the CO2-sensitive olfactory neuron is also a sensitive detector of human skin odorants in both Aedes aegypti and Anopheles gambiae. We demonstrate that activity of this neuron is important for attraction to skin odor, establishing it as a key target for intervention. We screen ∼0.5 million compounds in silico and identify several CO2 receptor ligands, including an antagonist that reduces attraction to skin and an agonist that lures mosquitoes to traps as effectively as CO2. Analysis of the CO2 receptor ligand space provides a foundation for understanding mosquito host-seeking behavior and identifies odors that are potentially safe, pleasant, and affordable for use in a new generation of mosquito control strategies worldwide.
Mosquitoes transmit deadly pathogens like malaria parasites, dengue viruses, and filarial worms to hundreds of millions of people every year. Female mosquitoes use two volatile cues to select and navigate toward hosts: exhaled CO2 and human skin odorants (Cardé and Gibson, 2010,Dekker and Cardé, 2011,Dekker et al., 2005,Gillies, 1980,Mboera et al., 2000). Host preference and host-seeking ability play pivotal roles in disease transmission and are targets for intervention.
Female mosquitoes detect plumes of exhaled CO2 using a class of olfactory receptor neurons (ORNs) designated cpA. CpA neurons are housed in capitate peg(cp) sensilla on the maxillary palps and express the CO2 receptor, comprising three conserved members of the Gustatory receptor (Gr) gene family (designatedGr1, Gr2, and Gr3 in most mosquitoes or Gr22, Gr23, and Gr24 in A. gambiae) (Figure 1A) (Grant and O’Connell, 1996,Jones et al., 2007,Lu et al., 2007,Robertson and Kent, 2009,Syed and Leal, 2007). A host-seeking female will fly upwind when these neurons are activated, toward a CO2 source in a laboratory arena or to CO2-baited traps in the field (Cooperband and Cardé, 2006,Dekker et al., 2005,Healy and Copland, 1995,Lacey and Cardé, 2011,Xue et al., 2008). Conversely, preventing cpA from detecting changes in CO2 dramatically reduces attraction toward CO2 sources (Erdelyan et al., 2012,Turner et al., 2011).
The role of human odor in host seeking is more complex since it is a blend of hundreds of volatiles from skin, sweat, and associated microbiota (Bernier et al., 2000,Dormont et al., 2013,Gallagher et al., 2008) (see for more references). ORNs in the antennae and palps express members of the Or and IR chemoreceptor families (Kwon et al., 2006,Lu et al., 2007,Pitts et al., 2011,Qiu et al., 2006,Syed and Leal, 2007) that respond to some skin odorants and are candidates for contributing to skin attraction (Carey et al., 2010,Wang et al., 2010). Other studies on antennal or maxillary palp sensilla have also identified activating odorants from skin (Ghaninia et al., 2008,Qiu et al., 2006,Syed and Leal, 2007). However, a causal relationship between activity of particular receptors or neuron classes and behavioral attraction has not been established as with the cpA neuron and CO2. Of the odorants that have been tested, a small number, such as lactic acid, ammonia, carboxylic acids, 1-octen-3-ol, and nonanal, increase mosquito attraction when presented together with CO2, but these are poor attractants by themselves (Njiru et al., 2006,Qiu et al., 2007,Syed and Leal, 2009), reviewed in Smallegange and Takken, 2010. Mosquitoes are nonetheless attracted to whole skin odor even in the absence of CO2 (Geier et al., 1999,Lacey and Cardé, 2011,Njiru et al., 2006,Schreck et al., 1981,Smallegange et al., 2010a). Intriguingly, mosquitoes that lack the coreceptor orco, and so lack functional Or receptors, are still attracted strongly to human skin odor with CO2 (DeGennaro et al., 2013), suggesting that other receptors may also play a role in skin attraction.
Here, we show that the CO2-sensitive, Gr-expressing cpA olfactory neurons on the maxillary palps of mosquitoes are also sensitive detectors of human skin odor, a function conserved in A. aegypti and A. gambiae. We use a novel chemical strategy to selectively knock down cpA responses to skin odor and demonstrate that this neuronal pathway is also important for attraction to skin odor in a wind tunnel. The role of this neuron class in host-seeking behavior toward both CO2 and skin odor establishes it as the key target for behavioral intervention. We screen ∼0.5 million compounds in silico to identify new receptor ligands that modify mosquito behavior, including a cpA antagonist that reduces attraction to skin and an agonist that lures mosquitoes as effectively as CO2. We demonstrate inDrosophila melanogaster that neuronal response and aversive behavior to a structurally diverse panel of odorants depends on the highly conserved CO2receptor. Our analysis of the CO2 neuron ligand space provides a foundation for understanding mosquito host-seeking behavior and the chemical basis of host attractiveness and identifies odors that are safe, pleasant, and affordable for immediate use in mosquito control.
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