On a still night, as the air is thick with silence, the sharp, whining buzz of a mosquito shatters the calm. These blood-sucking insects that disturb people’s deep slumber are also responsible for spreading diseases such as dengue, chikungunya, malaria and Zika fever, which affect millions of people each year worldwide.

Given the harmful effects of pesticides on the environment, combined  with the emergence of mosquitoes resistant to pesticides, scientists are looking for alternative environment-friendly approaches for pest management.^1,2 

Now, researchers have developed a new population control method where male insects carrying toxic proteins can poison disease-spreading females during mating.³ The results, published in Nature Communications, describe a genetic biocontrol method that offers a fast and effective solution to managing pests.

Such approaches are not entirely new. In the 1950s, when researchers mated female insects with radiologically sterilized males, they did not produce offsprings, reducing the next generation’s population.⁴  More recently, scientists propagated transgenes in insects that lower the fitness of future generations, resulting in decreased insect population.⁵ Although such methods are promising, they require at least one generation to take effect: Female insects may not produce offsprings, but they can continue transmitting infections.⁶ 

“As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” said study author Samuel Beach, a graduate student in biologist Maciej Maselko’s lab at Macquarie University, in a press release. 

Beach and Maselko explored whether they could target disease-spreading female insects. Other researchers had previously used proteins in the semen of males to reduce the fitness and fertility in their female mates.⁷ This physiological response is caused by seminal fluid proteins, produced in male accessory glands, which get transferred to females along with sperm during mating. 

Based on these data, the researchers set out to identify proteins that would be toxic to only female insects and have no effect in mammals. Using databases like FlyAtlas 2, the researchers narrowed down a handful of insect-specific venom proteins from spiders and sea anemones.⁸  

Beach and Maselko used the fly Drosophila melanogaster to test the proof of concept of the method they dubbed toxic male technique (TMT). They genetically engineered male flies to produce the insecticidal proteins in their reproductive tracts (TMT males). The researchers investigated how the expression of toxic proteins affected the male flies’ longevity. While male flies carrying spider venom proteins lived as long as wild type flies, those carrying sea anemone venom proteins had a reduced lifespan. However, courtship assays revealed that expressing these venom proteins did not alter the male flies’ ability to court with females.

Encouraged by these results, the researchers mated TMT males carrying either spider or sea anemone venom with female flies. Longevity assays revealed that females mated with TMT males had a significantly reduced lifespan compared to females mated with wild type males. 

The researchers next sought to evaluate how this genetic biocontrol approach might compare to currently used pest control techniques. They developed computer models to simulate conventional interventions and TMT to predict their ability to suppress populations of Aedes aegypti, a mosquito species that transmits dengue and Zika fever. The models predicted that compared to conventional techniques, applying the new approach could significantly reduce blood-feeding rates, which can reduce disease transmission. 

While this indicates that applying TMT into mosquitoes is probable, the researchers noted the need to test this thoroughly. “We still need to implement it in mosquitoes and conduct rigorous safety testing to ensure there are no risks to humans or other non-target species,” said Maselko.