Malaria: Mosquito vs. Fungus

In several regions of sub-Saharan Africa where malaria is endemic, mosquitoes have become increasingly resistant to traditional chemical pestisides. Several species of Plasmodium, the parasitic protozoans that cause malaria are also becoming increasingly resistent to the medication we use to treat patients. What we have here is a potential perfect storm.
Researchers needed to think of new ways to combat the mosquito and the disease causing organism. Enter a fungus with the scientific name Metarhizium pingshaense[1]. The wild-type Metarhizium pingshaense strain has a narrow host range: just two disease-carrying mosquito species Anopheles gambiae and Aedes aegypti. It penetrates the mosquito’s exoskeleton and gradually killing it from the inside out.

Normally, high doses of spores and long periods of time are required for regular Metarhizium pingshaense to kill the mosquito. 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.

“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.
The team concluded the most effective strain should contain two toxins – one derived from the North African desert scorpion (Androctonus australis) and the other from the Australian Blue Mountains funnel-web spider (Hadronyche versuta).

The researchers also took care to ensure their anti-malarial 'spiderman' would not become an environmental problem. 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.

[1] Bilgo et al: Improved efficacy of an arthropod toxin expressing fungus against insecticide-resistant malaria-vector mosquitoes in Scientific Reports – 2017. See here.

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