Genetic Biocontrol Shortens Female Mosquito Lifespan to Fight Disease

Researchers at Applied BioSciences at Macquarie University and the ARC Centre of Excellence in Synthetic Biology at Macquarie University have developed a biological pest control method that targets the lifespan of female insects, which they suggest could be used to significantly reduce the threat of insect pests such as disease-carrying mosquitoes. The new genetic biocontrol approach, known as the toxic male technique (TMT), involves genetically engineering male insects to produce insect-specific venom proteins in their semen. When these engineered males then mate with females the proteins are transferred, significantly reducing female lifespan and so their ability to spread disease.

In a study reported in Nature Communications and titled, “Recombinant venom proteins in insect seminal fluid reduce female lifespan”, Samuel J. Beach, PhD, and Maciej Maselko, PhD, demonstrated TMT in Drosophila melanogaster males, which reduced the lifespan of mated females by up to 64% compared with control females mated with wild-type males. In their paper, the team concluded that their results “… demonstrate the potential of TMT as the next generation of genetic biocontrol, which is especially suited to rapidly respond to outbreaks of disease vectors and agricultural pests.”

Insect pests pose a growing threat to global health and agriculture, causing hundreds of thousands of deaths, millions of infections, and costing billions in healthcare and crop damage annually, the authors wrote. “Malaria, spread by several species of Anopheles mosquitoes, causes 608,000 deaths per year and rates of arboviral diseases spread primarily by the Aedes aegypti mosquito, including dengue, Zika, chikungunya, and yellow fever, are reaching unprecedented levels due to increased global trade and warming climates,” the authors wrote. “Dengue virus alone causes 390 million human infections each year and is now considered the most common vector-borne viral infection worldwide.”

Pesticides are the first line of defense against many invasive species, particularly mosquitoes, the researchers noted. However, overreliance on insecticides has resulted in the widespread emergence of resistance, and pesticides also impact non-target species and ecosystems. “Modern integrated pest management is trending toward reducing reliance on chemical insecticides in favor of other environmentally friendly management techniques to reduce the emergence of resistances.”

Genetic biocontrol has emerged as a promising alternative to insecticides, the researchers continued. Genetic biocontrol is defined as “the release of organisms which have been genetically altered to reduce the spread and harm caused by a target species …”  In mosquitoes such as Aedes aegypti and Anopheles gambiae, only the females bite and transmit diseases. Current genetic biocontrol technologies (GBT), such as sterile insect technique (SIT) or the release of insects carrying a dominant lethal gene (RIDL), work by releasing massive numbers of sterilized or genetically modified males to mate with the wild females.

The mated females produce no offspring or only male offspring, but they continue to bloodfeed and spread disease until they die naturally—meaning that populations of biting females only decrease when the next generation emerges. As the authors noted, “… all current mating-based genetic biocontrol technologies function by releasing engineered males which skew sex-ratios or reduce offspring viability in subsequent generations which leaves mated females to continue to cause harm (e.g., transmit disease) … Currently, all GBT require a minimum of a generation to take effect on the target population and often much longer until the harm from a pest outbreak is mitigated.”

An alternative approach to genetic biocontrol that has been considered is the potential use of seminal fluid proteins (SFP), which are produced within the male accessory glands (MAG) and stored in the male until they are transferred to females along with sperm and other compounds. The newly reported toxic male technique involves genetically engineering the male to express toxic compounds within the MAG, which are then transferred to the female during mating, reducing female lifespan. The team said this approach is, to the best of their knowledge, “… the first example of an intragenerational GBT.”

By immediately reducing the biting female population, TMT could offer significant advantages over competing genetic biocontrol methods, the researchers suggested. “As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” said lead author Beach. “By targeting the female mosquitoes themselves rather than their offspring, TMT is the first biocontrol technology that could work as quickly as pesticides without also harming beneficial species.”

In their reported study, the team carried out laboratory tests using fruit flies (Drosophila melanogaster). They engineered the males to express one of a number of insect-specific venom proteins in a MAG-specific pattern., and demonstrated that females mated with the TMT males had lifespans shortened by 37–64% compared to those mated with unmodified males.

Computer models predicted that applying TMT to Aedes aegypti, a highly aggressive mosquito species primarily responsible for transmitting Dengue and Zika, could reduce blood-feeding rates—a key factor in disease transmission—by 40–60% compared to established methods.

Safety and environmental safety are central to the TMT approach. Venoms naturally contain a mixture of many proteins, and the targets of those used in TMT are only present within invertebrates, so are not toxic to mammals, and unlikely to cause harm when consumed by beneficial insects, since their oral toxicity is also very low. “This innovative solution could transform how we manage pests, offering hope for healthier communities and a more sustainable future,” suggested Beach.

The reported study was performed in associate professor Maselko’s lab and provides the proof of concept for this breakthrough approach to suppressing the populations of pest species. ‘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,” Maselko acknowledged.

In their paper, the team concluded, “The development of intragenerational genetic biocontrol technologies such as TMT represents a paradigmatic shift in pest management. Relative to current biocontrol technologies, the speed of population suppression achievable by intragenerational biocontrol may make these techniques a viable alternative to chemical pesticides as a first-line response to outbreaks while retaining taxonomic specificity and reducing off-target effects on local ecologies.”