Mosquitoes placed in a container. [Credit: Mark Sherwood and Raymond St. Leger.]Mosquitoes placed in a container. [Mark Sherwood and Raymond St. Leger]

In the battle against mosquito-borne diseases that kill hundreds of thousands of people each year, scientists turned to an unlikely ally, an engineered fungus that smells like flowers. Taking advantage of the mosquito’s natural attraction to flowers, the international research team engineered a strain of Metarhizium fungus—the spores of which are deadly to mosquitos—that imitates a flower’s sweet scent and so lures mosquitoes to their deaths. The scientists say their achievement offers new hope against mosquito-borne diseases such as malaria and dengue, which traditional methods such as chemical pesticides can no longer control.

“Mosquitoes need flowers because they provide nectar, a crucial source of food for them, and they are drawn to flowers through their scents,” explained paper co-corresponding author Raymond St. Leger, PhD, a Distinguished University professor of entomology at the University of Maryland. “After observing that some types of fungi could trick mosquitoes into thinking they were flowers, we realized we could turbo-charge the attraction by engineering fungi to produce more longifolene, a sweet-smelling compound that’s already very common in nature. Before this study, longifolene wasn’t known to attract mosquitoes. We’re letting nature give us a hint to tell us what works against mosquitoes.”

St. Leger, together with co-senior and co-corresponding author Weiguo Fang, PhD, at Zhejiang University, Hangzhou, and colleagues reported on their work in Nature Microbiology, in a paper titled “Engineered Metarhizium fungi produce longifolene to attract and kill mosquitoes,” in which they wrote in summary, “… a strain of M. pingshaense, a virulent mosquito pathogen, was engineered to have attractive spores that can be mass produced using inexpensive media. These spores serve as both lure and mycoinsecticide, effectively eliminating mosquitoes.”

Mosquitoes are the most dangerous animals on earth, with an estimated two billion people at risk of serious mosquito-borne diseases including malaria, dengue, and chikungunya, the authors reported. And while chemical insecticides have been the primary method used for mosquito control, mosquitoes have gained enough resistance to the compounds to render insecticides ineffective. “Metarhizium fungi are emerging as promising alternatives owing to their eco-friendly nature and efficacy against insecticide-resistant mosquitoes, even increasing their susceptibility to chemical insecticides,” the authors further noted.

Such fungi can kill mosquitoes with just a small number of spores. “It was previously shown that caterpillars affected by fungal infections can attract mosquitoes,” they pointed out. “However, the mechanisms and potential applications of this attraction are lacking.”

Through their newly reported study the team found how Metarhizium fungi can attract draw insect prey to promote spore dispersal. “… we show that Metarhizium-colonized insect cadavers release the volatile longifolene to attract and infect healthy insects, facilitating spore dispersal,” they noted. The scientists also identified in the fruit fly Drosophila melanogaster and in the mosquito Aedes albopictus the receptor for the odorant. They then engineered the Metarhizium fungus to create a strain, Mp-Tps, that releases longifolene as a deadly perfume to attract mosquitoes. “The virulent mosquito pathogen Metarhizium pingshaense was engineered to express pine longifolene synthase to produce a large amount of longifolene …” they explained. “The transgenic spores effectively attracted and killed male and female A. albopictus, Anopheles sinensis, and Culex pipiens.

St. Leger noted that the floral-scented fungus is an easy-to-use control method against mosquitoes, requiring little to no training or specialized knowledge. As soon as the fungus spores are placed in a container, either indoors or outdoors, longifolene is instantly and gradually released, maintaining effectiveness for months. Once mosquitoes encounter the fungus, they become infected and die within days.

Although the fragrant fungus is deadly to mosquitoes, it is harmless to humans. In reported lab tests, the fungus killed 90 to 100% of mosquitoes—even when placed in a large room with competing scents from humans and real flowers. “We showed that the transgenic strain Mp-Tps efficiently controlled wild-caught mosquitoes in a large room with humans or mosquito-attracting plants,” they noted.

“The fungus is completely harmless to humans as longifolene is already commonly used in perfumes and has a long safety record,” St. Leger said. “This makes it much safer than many chemical pesticides. We’ve also designed the fungus and its containers to target mosquitoes specifically rather than any other insects and longifolene breaks down naturally in the environment.”

In addition, unlike chemical alternatives to which mosquitoes have gradually become resistant, this biological approach may be nearly impossible for mosquitoes to outsmart or avoid. “If mosquitoes evolve to avoid longifolene, that could mean they’ll stop responding to flowers,” St. Leger explained. “But they need flowers as a food source to survive, so it would be very interesting to see how they could possibly avoid the fungus yet still be attracted to the flowers they need. It’ll be very difficult for them to overcome that hurdle, and we have the option of engineering the fungus to produce additional floral odors if they evolve to specifically avoid longifolene.”

What also makes this new fungal technology particularly promising is how practical and affordable it is to produce. Other forms of Metarhizium are already commonly cultivated around the world on cheap materials like chicken droppings, rice husks and wheat scraps that are readily available after harvest. The affordability and simplicity of the fungus could be key to reducing mosquito disease-related deaths in many parts of the world, especially in poorer countries in the Global South.

Finding effective new weapons against mosquitoes could be more important than ever. St. Leger warns that in the future, mosquito-borne diseases currently limited to tropical regions could threaten new targets, including the United States. With rising global temperatures and the growing unpredictability of weather, disease-carrying mosquitoes have begun to spread to new areas beyond their usual habitats. “Mosquitoes love many of the ways we are changing our world,” St. Leger said. “Right now, we’re hoping to use these approaches in Africa, Asia, and South America. But one day, we may need them for ourselves.”

The team does note that unlike their laboratory simulations, real mosquito environments are more complex. “In future, field trials will be necessary to comprehensively assess its mosquito control efficacy and inform further research for developing efficient and safe Mp-Tps-based mosquito control agents,” they wrote. St. Leger and his collaborators are currently working on larger-scale outdoor trials of their mosquito control method to submit for regulatory approval.

“It’s not as if you’re going to necessarily find a silver bullet to control mosquitoes everywhere, but we’re trying to develop a very diverse and flexible set of tools that people in different parts of the world can use and choose from,” St. Leger said. “Different people will find different approaches work best for their particular situation and the particular mosquitoes they’re dealing with. In the end, our goal is to give people as many options as possible to save lives.”