Transgenic fungus shows huge promise for malaria control in West Africa

By Mark Lynas

May 31, 2019

A fungus genetically engineered to express a spider venom can successfully control populations of malarial mosquitoes, a new study suggests.

In a new paper published May 30 in the journal Science, a team of researchers from the University of Maryland and Burkina Faso describe the results of an outdoor trial aiming to test the efficacy of their transgenic fungus in environmental conditions.

They found that the fungus — a version of naturally-occurring Metarhizium pingshaense engineered to express an insect-killing toxin produced by the Australian Blue Mountains funnel-web spider — reduced populations of mosquitoes by more than 99 percent.

The trials were conducted in a specially-built simulated village — dubbed the MosquitoSphere by the scientists — complete with huts and muddy pools for the mosquitoes to breed in, all enclosed by a double-layer of mosquito netting to prevent the blood-sucking insects from escaping.

“Simply applying the transgenic fungus to a sheet that we hung on a wall in our study area caused the mosquito populations to crash within 45 days,” said Brian Lovett, a graduate entomology student who is lead author of the new paper.

There were 219 million malaria cases worldwide in 2017, according to the World Health Organization (WHO), and they  caused 435,000 deaths, mainly of children under five. The WHO warns that there has been “no significant progress in reducing global malaria cases” in recent years.

One of the main reasons for this lack of progress is that malaria-carrying mosquitoes are becoming increasingly resistant to the insecticides that are sprayed on bed nets and around dwellings in an effort to control their populations.

Insecticides can also have toxic effects on human health and the environment, further spurring efforts to find alternative methods of controlling malaria. Reassuringly, Lovett reports that he found the GM fungus “is as effective at killing insecticide-resistant mosquitoes as non-resistant ones.”

Burkina Faso alone had nearly 8 million cases of malaria in 2017 and is one of 10 high-burden countries that are not on track to meet their WHO malaria control targets.

The fungus used by the researchers, Metarhizium pingshaense, is a naturally-occurring pathogen that infects insects in the wild and has been used to control pests for centuries.

The scientists used a strain of the fungus that is specific to mosquitoes and engineered it to produce a toxin that increased the virulence of the pathogen so that it could kill the insects faster than they can breed, thereby reduce mosquito populations. The new version was termed Mp-Hybrid.

“You can think of the fungus as a hypodermic needle we use to deliver a potent insect-specific toxin into the mosquito,” said Raymond St. Leger, distinguished professor of entomology at the University of Maryland.

In a previous study the researchers tested the fungus on bees to check if its effects would be limited to malarial mosquitoes and not affect other insects. Local honeybees were deliberately infected with fungal spores, but none were infected or died during two weeks of close monitoring.

Another safeguard has been added with the use of genetic sequence ensuring that the spider venom is only expressed by the fungus once it is inside the bloodstream of a mosquito insect.

“The toxins we’re using are potent, but totally specific to insects. They are only expressed by the fungus when in an insect. Additionally, the fungus does nothing at all to bees and other beneficial species,” St. Leger said after the earlier study. “So we have several different layers of biosecurity at work.”

The researchers also point out in the Science paper that “substantial off-site dispersal of Mp-Hybrid is unlikely given that its large, sticky, ultraviolet light–sensitive spores do not naturally become airborne, and application methods such as the attachment of spores to sheets in residential use sites can further reduce opportunities for movement.”

The spider venom toxin has additionally already been approved by the US Environmental Protection Agency for outdoor use as a biopesticide to control lepidopteran (moths and butterflies) pests.

The use of transgenic fungus is one of many innovative approaches to combating mosquitoes using biology. The UK-based company Oxitec has been engineering mosquitoes with a sterility gene in order to reduce transmission of dengue and Zika virus diseases in South America.

Another approach has been to use the Wolbachia bacteria, introducing it into pathogen-carrying mosquitoes in order to prevent them transmitting diseases such as Zika, dengue, chikungunya and yellow fever.

Gene drives have also been proposed as a way of controlling mosquitoes, specifically the Anopheles species that mostly transmit malaria. An organization called Target Malaria is working in West Africa on genetic engineering approaches to reduce the fertility of Anopheles or their ability to transmit disease.

However, one of the biggest threats to these programs is fears stirred up by anti-GMO groups, which might lead to bans on disease control in the same way that GMO bans have hampered the development of agricultural biotechnology around the world.

As Professor Michael Bonsall, a University of Oxford scientist who was not involved with the study, commented: “Proportionate bio-safety regulations are needed to ensure that the viability of this and other approaches for vector [mosquito] control using genetic methods are not lost through overly zealous restrictions.”

“By following EPA and World Health Organization protocols very closely, working with the central and local government to meet their criteria and working with local communities to gain acceptance, we’ve broken through a barrier,” lead author Lovett concluded. “Our results will have broad implications for any project proposing to scale up new, complex and potentially controversial technologies for malaria eradication.”