Fighting malaria with fungi: biologists engineer a fungus to be deadlier to mosquitoes

Bed nets. Insecticides. Sterile and genetically modified insects. Now scientists are adding a genetically engineered toxic fungus to the arsenal of weapons to wipe out mosquitoes that carry the malaria parasite.

Although insecticides and insecticide-laced bed nets, by far the two most commonly employed strategies, have effectively lowered the numbers of infections and deaths, the global malaria burden has failed to decline in the last few years. In 2017, 219 million people were infected with malaria and an estimated 435,000 died. That is because mosquitoes are evolving resistance to insecticides.

An Anopheles mosquito taking a blood meal from a human host. It is in the course of these blood meals that mosquitoes transmit malaria to humans. CDC
The rapid evolution of resistance is a common and recurrent theme in our arms races against malaria transmitting mosquitoes, as well as against pests and pathogens in general. Over time, organisms mutate and evolve resistance to any new drug that is used to kill them. No wonder humans always end up on the losing side; that’s why a new weapon is needed. And the latest one is a killer fungus.

Fighting killers with killers

As an evolutionary biologist studying fungi, I am familiar with the ability of these organisms to cause devastating diseases in diverse plants and animals, including humans. While many fungal pathogens infect a broad range of hosts, others can attack only a select few.

This realization has led scientists to a new strategy for fighting malaria: infect and kill disease-transmitting mosquitoes using fungal pathogens that they encounter in nature. This isn’t the first time that fungi have been weaponized. In fact, this is precisely the strategy behind the highly successful biological pesticide, Green Muscle, which kills locusts and grasshoppers around the world.

Infecting mosquitoes with their natural pathogens – such as the pathogenic fungi from the genus Metarhizium – is a particularly attractive strategy because, unlike bacterial or viral pathogens, fungi can infect mosquitoes simply by coming into contact with them and don’t have to be ingested. Also, fungi are generally friendlier to the environment than traditional chemical insecticides. But does this strategy work?

Fifteen years ago, a field trial in rural Tanzania showed that it could. By hanging cotton sheets inoculated with insect-killing fungi on the ceilings of houses where mosquitoes rest, one-third of mosquitoes became infected. According to malaria transmission models, such an infection rate could reduce malaria cases by 75%.

But Metarhizium fungi, as the Tanzanian field trial showed, are not always capable of infecting their mosquito hosts. And, fungal infections typically take several days to kill mosquitoes. In the lab, fungi take an average of between seven and nine days to kill the mosquitoes, depending on the dose. Brian Lovett, a graduate student working in Ray St. Leger’s lab, and Etienne Bilgo, a post-doctoral fellow working with entomologist Abdoulaye Diabate, thought they could infect more mosquitoes and kill them faster.

How? By using fungi that had been genetically modified to produce a toxin called “Hybrid,” which specifically attacks the nervous system of arthropods, a group that includes insects and their kin, like spiders and crustaceans. Previous laboratory experiments in 2017 by the same team had already shown that these GM fungi killed mosquitoes quicker than unmodified ones.