Fungi Join the Fight Against Malaria

SLAP. You’re sitting outside at a summer bonfire and you catch a mosquito feasting on your leg. Groaning, you realize this probably means a couple days of itching and a swollen welt. Usually in North Carolina, you’re going to be just fine and should only seek medical attention if you experience complications. However, for many, particularly in Sub-Saharan Africa, a mosquito bite can mean something particularly dangerous: the possibility of infection with malaria.

Cells infected with Plasmodium falciparum possess characteristic purple dots, often connected in a “headphones” shape. Source: Steven Glenn, Laboratory and Consultation Division, USCDCP (PIXIO)

Malaria is a parasitic infection caused by Plasmodium falciparum, a single-celled organism that lives in the salivary gland of Aedes aegypti mosquitoes and is considered the deadliest human parasite. The World Health Organization reported in 2018 that progress in reducing cases of malaria globally has stalled, with nearly 435,000 people, primarily Sub-Saharan African children, dying from the disease per year. Much of this lack of progress can be attributed to mosquitoes developing a tolerance for commonly used chemical insecticides. Recent work from scientists at the University of Maryland in collaboration with researchers in Burkina Faso has hacked biology to create a new tool to combat the problem of malaria-carrying mosquitoes. The tool? Genetically modified fungus that wipes out mosquitoes with a deadly dose of spider toxin.

To develop their tool, the researchers used a type of fungus that already occurs in malaria-affected areas and targets mosquitoes: Metarhizium pingshaense. This species of fungus is entomopathogenic, which means that the fungus is a parasite to insect hosts and kills or disables them. In the wild, this fungus can kill mosquitoes, albeit quite slowly. It takes over a week in the lab for Metarhizium to kill a mosquito, by which time the mosquito could spread malaria and reproduce. To speed up the process, the scientists used genetic engineering to give Metarhizium a deadly tool: a gene from the Australian Blue Mountains Funnel-web spider that creates a potent toxin. In the wild, the spider’s fangs deliver a neurotoxin that disrupts the way neurons send signals in the brain. This causes symptoms including dangerously elevated heart rate and blood pressure and difficulty breathing. If bitten by a funnel web spider, death can occur in humans rapidly. However, to ensure the toxin only affects mosquitos, the scientists disabled the toxin from being made by the fungus until the right moment — when the fungus reaches the bloodstream of the mosquito.

The Australian Funnel Web spider is considered to be one of the deadliest spiders on Earth. Source: Brenda Clarke (flickr)
A cockroach infected with a species of Metarhizium. Source: Chengshu Wang and Yuxian Xia, PLoS Genetics Jan. 2011 (Wikimedia Creative Commons)

The fungus was tested in a unique environment in Burkina Faso: the MosquitoSphere, an enclosure where genetically modified organisms are permitted to be tested.

To conduct the experiment, two populations of 1500 mosquitoes were released in the MosquitoSphere. To expose the insects to the fungus, the investigators mixed the Metarhizium spores with sesame oil and spread the mixture onto black cotton sheets. When mosquitoes landed on the sheets, they were exposed to the toxic fungal spores. The mosquito population exposed to the unmodified Metarhizium had no problem reproducing before the fungus proved fatal, with their population totaling nearly 2500 after 45 days. In contrast, the population of mosquitoes exposed to the genetically modified Metarhizium after 45 days shrunk to a mere 13 individuals. A population of 13 mosquitoes indicated that the mosquitoes were dying more quickly than they could breed, therefore producing an unsustainable, or collapsed population. The striking results of the experiments in the MosquitoSphere encouraged the investigators to conclude that the genetically modified Metarhizium can function as a potent mosquito-killing bio-pesticide and cause an interbreeding colony of mosquitoes to collapse in a little over a month.

Despite success in the MosquitoSphere, the fungus still needs to undergo more testing to be considered safe for humans and the environment. If it is approved, a formulation of the fungal spores could be used to protect dwellings and mosquito netting from malaria-carrying mosquitoes. This study is a promising sign for the use of genetically modified bio-pesticides to wipe out disease-causing insects, which could prove invaluable for malaria prevention. 

Peer editor: Elise Hickman