Soft, high-pitched murmurs. The itch that follows. It’s that time of the year when we battle against mosquito bites. But irritation is not the only thing we have to fight. Malaria and Dengue fever are examples of mosquito-borne diseases that affect hundreds of millions each year. Female mosquitoes act as vectors that transmit pathogens through feeding on our blood.

Here is another reason for you to hate mosquitoes: they pee on you. This, however, is not an act of insult, but a biological necessity. As a mosquito sucks blood, it needs to get rid of the excess fluid. Blood also contains surplus of salts that must be expelled. Through urination, the mosquito can maintain the balance of fluid and salt in its body. Researchers are using this trait in hopes of bring about the mosquitoes’ doom.

Currently available insecticides for mosquitoes, such as DDT and pyrethroids, primarily target the nervous system. No new mosquito insecticides have been developed in over 30 years, and drug resistance is emerging. This is a dire situation for preventing the spread of mosquito-borne diseases. A research team led by Peter Piermarini from Ohio Agricultural Research and Development Center, Ohio State University, is exploring a new target for mosquito insecticides: urine excretion. This approach is especially effective against female mosquitoes carrying eggs that prey upon blood.

In a study published last year, Piermarini and his team examined the effect of a small molecule, called VU573, that prevents urine excretion through kidney failure. When this chemical is injected into female mosquitoes, urine production and excretion are disrupted and results in “detrimental consequences,” namely inability to fly, and sometimes death. The treated mosquitoes all have “bloated” abdomen due to the buildup of fluid.

The researchers suggest that flightless, bloated mosquitoes “…would decrease their reproductive output and ability to transmit pathogens by limiting the number of vertebrate blood meals they could consume.” “Therefore, such inhibitors could be considered as a potential new class of insecticides to be further developed for combatting the emerging problem of insecticide resistance in mosquitoes,” the investigators conclude at the end of the study.

The two main challenges that remain to be tackled before the new insecticides can be developed are to fine-tune the specificity and to develop effective delivery system into mosquitoes. VU573 molecule was initially identified as a blocker against mammalian proteins. Needless to say, new insecticides must be able to selectively target mosquitoes and be harmless to humans and other beneficial insects, such as bees. The insecticides also must be able to penetrate mosquitoes without the need for manual injections.

The scientists are continuing their endeavors to overcome these challenges. In another report published last month, the same research team investigates another small molecule, VU590, that also disrupts urine excretion in mosquitoes but at much higher potency and specificity. (Although the names suggest the two molecules are similar, VU590 is structurally unrelated to VU573.) Injection of VU590 into female mosquitoes causes abdominal bloating but, unlike VU573, “…leads to outright death within 24 [hours] without obvious sub-lethal effects, such as the loss of flight,” the researchers observe. “In conclusion, the present study validates [urine excretion] as an insecticide target and confirms that small molecule modulators [that cause kidney failure] offer valuable new active compounds for insecticide development,” Piermarini and his team comment.

Both reports [1,2] are published in PLoS One and are freely available to the public (open access).

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