Mutant fungus uses venom to kill malaria mosquitos

A female anopheles gambiae mosquito killed by the engineered metarhizium pingshaense. The fungus is also engineered to express a green fluorescent protein for easy identification of the toxin-producing fungal structures.
A female Anopheles gambiae mosquito killed by the engineered Metarhizium pingshaensei. The fungus is also engineered to express a green fluorescent protein for easy identification of the toxin-producing fungal structures.
Credit: Brian Lovett

In the global war against insecticide-resistant malaria-carrying mosquitos, a new super weapon may be at hand: an unassuming fungus.

A research team from the University of Maryland has genetically engineered a fungus with spider and scorpion toxins to enhance its artillery and boost its mosquito-killing power.

In some of the most devastatingly malaria-struck regions of sub-Saharan Africa, mosquitos that carry the malaria parasite have become resistant to traditional chemical pesticides. This has left scientists on a desperate hunt for alternative ways to combat the disease responsible for the death of nearly half a million people each year worldwide.

The recent research, published in Scientific Reports, began with the fungus Metarhizium pingshaensei, which in its natural state already kills of the two disease-carrying mosquito species Anopheles gambiae and Aedes aegypti. Its gruesome mechanism of action entails penetrating the mosquito’s exoskeleton and gradually killing it from the inside out.

Sounds pretty deadly, so why does it need to be turbocharged? It’s a question of quantity, rather than quality. High doses of spores and long periods of time are required for natural Metarhizium to get the job done.

The researchers therefore decided to give the fungus a genetic makeover, pasting in several new genes expressing neurotoxins derived from both spider and scorpion venom.

These toxins act by blocking ion channels integral to the transmission of nerve impulses, thereby effectively paralysing their victims.

This innovative tactic of combating insecticide resistant malaria functions by differentially targeting ion channels.

“Unlike chemical insecticides that target only sodium channels, many spider and scorpion toxins hit the nervous system’s calcium and potassium ion channels, so insects have no pre-existing resistance,” explains senior author Professor Raymond St. Leger.

Following numerous rounds of testing, while several engineered strains of fungus displayed enhanced mosquito lethality compared to the unaltered counterpart, the team concluded the most effective strain contained two toxins – one derived from the North African desert scorpion and the other from the Australian Blue Mountains funnel-web spider Hadronyche versuta.

The researchers also took care to ensure their anti-malarial superhero would not become an environmental villain.

To keep the potent toxins from disseminating into the broader environment, the team attached a highly specific promotor sequence of DNA to the toxin genes, acting as a genetic “switch” to ensure the expression of the toxins was only triggered once in the blood of an insect.

The next step is to expand testing from custom-built greenhouse-like enclosures in Burkina Faso to deploying the spores in field tests, and eventually to use on wild mosquito populations.

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