Fungus loaded with scorpion toxin to fight malaria

By Ed Yong | February 24, 2011 2:00 pm

Meet our newest potential weapon against malaria – a fungus loaded with a chemical found in scorpion venom. Metarhizium anisopliae is a parasitic fungus that infects a wide variety of insects, including the mosquitoes that spread malaria. Their spores germinate upon contact and the fungus invades the insect’s body, slowly killing it. Now, Weiguo Fang from the University of Maryland has modified the fungus to target the malaria parasites lurking inside the mosquitoes.

Fang loaded the fungus with two chemicals that attack the malaria parasite Plasmodium falciparum. The first is a protein called SM1 that prevents the parasites from attaching to the mosquito’s salivary glands. By blocking Plasmodium‘s path, SM1 stops the parasite from travelling down the mosquito’s mouthparts into the people it bites. The second chemical is scorpine – a toxic protein wielded by the emperor scorpion, which kills both bacteria and Plasmodium. This double whammy of biological weapons slashed the number of parasites in mosquito saliva by 98%.

Fang’s group is one of many who are trying to exploit fungi in the battle against malaria. These efforts are sorely needed. For decades, insecticides have been the mainstays of malaria control but mosquitoes have increasingly evolved to resist them. With few new chemicals on the horizon, biological weapons like fungi could be a decent replacement.

Fungal spores can be sprayed on surfaces, cloth and nets, where they can stay for months. Mosquitoes don’t need to ingest the spores to become infected. All it takes is a touch for the spores to germinate and penetrate the insect. In 2005, a British duo – Matt Thomas and Andrew Read – managed to kill more than 90% of malarial mosquitoes by spraying the fungi on surfaces. They reduced the number of insects that could transmit the disease by 80 times.

Later, Willem Takken from Wageningen University found that the fungi can also kill insecticide-resistant mosquitoes. They even make the insects vulnerable to insecticides once again. And just last week, Takken’s group used the fungal spores to kill mosquito larvae, which swim at the surface of stagnant water. They used a synthetic oil to spread the spores over the water. Compared to untreated spores, these oily ones halved the proportion of larvae that turned into adults.

So if natural fungi are so potent, why bother tweaking them? It’s all in the timing. The fungi need around two weeks to finish off a mosquito. It takes that long for malaria parasites to mature and enter the insect’s salivary glands, where they can move to another host. If the mosquitoes are infected with fungi soon after they pick up Plasmodium, they’ll die before they can pass them on. If they’re infected any later, they could still spread malaria before dying.

It’s possible to alter the fungus so it kills mosquitoes more quickly but this approach has its own problems. At the moment, the fungus only kills old mosquitoes, so it doesn’t really affect their chances of producing young. As a result, there’s little pressure on them to evolve resistance. That could change if the fungus starts killing mosquitoes earlier.

What you really want is a fungus that kills mosquitoes as slowly as the natural versions, but that stops them from passing on the malaria parasite in the meantime. That’s exactly what Fang created. He genetically engineered strains of the fungus to carry either SM1 (short for “salivary and midgut peptide 1”), scorpine, or a fusion of the two. He got the best results by pairing the fusion protein with pure scorpine. The latter killed the parasites outright, and the former prevented the few survivors from reaching the salivary glands.

The fungi slashed the insect’s ability to spread Plasmodium by five times, even if their malaria infections were very advanced. They successfully prevented the parasites from spreading while the host slowly died. But Takken isn’t convinced that this “interesting strategy” will do much good. “[It] would only be advantageous if one wants an immediate transmission-blocking effect. In practice, that will rarely be necessary,” he says. It might help against viral infections like yellow fever, which are also carried by mosquitoes but which spread more quickly than malaria.

Nor are the modified fungi without risks. M.anisopliae is fairly indiscriminate and can infect a variety of insects. In some ways, that’s promising because it could also be used to control tsetse flies, which spread sleeping sickness, and other species of mosquito that carry dengue fever and filariasis. On the other hand, the fungus could kill beneficial insects too. Fang thinks it should be possible to restrict the fungus to certain insect species by loading them with targeted antibodies.

Takken is also concerned about using a genetically engineered fungus. “I believe that it’s too early for such strategies as long as we have good methods for fungal mosquito control that do not require engineered fungal strains.” Read, now at Pennsylvania State University, has similar concerns. “We have so far barely scratched the surface of what is possible with natural fungal variation,” he says.

However, Read thinks that the modified fungus has potential. “The approach is very practical: fungal biopesticides are already produced and used in Africa for locust control,” he says. “Will the public be OK with having a GM product sprayed in their houses?” he asks. “My own view on this is that they should be. Up against malaria, hypothetical concerns about GM pale.”

Read says that the biggest hurdle is a lack of interest from funders, who are focused on chemical insecticides. “It remains to be seen whether they can be persuaded to take biologics seriously.  Perhaps this paper will help, although great ideas and great data, and even papers in Science, have not so far proved sufficient.”

Reference: Fang, Vega-Rodriguez, Ghosh, Jacobs-Lorena, Kang & St Leger. 2011. Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes. Science

Image from Rob Graham and Jon Darbro

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Comments (10)

  1. Bob Abela

    Gone are the days of DDT…such potential here. As for being an indiscriminate fungus…just as long as it doesn’t take a liking to people. :)

  2. zackoz

    Promising, but if the fungus were to attack bees, it would be a different story.

  3. Amazing. Out of interest do you have any idea if there might be any way to get fungus to attack mosquito-borne viruses?

  4. Jenjen

    This fungus itself has been implicated in a couple of reported cases of human infection, both in the eye. Of course nobody knows for sure what adding the toxins might do – I can imagine the spores might be kind of an inhalation problem if they are airborne, like they might be if they are liberally sprayed around sleeping quarters. But really, what could go wrong?

  5. Dan

    In reply to Jenjen, remember Murphy’s Law!

  6. DC

    I think like Jenjen says, that this is incredibly shortsighted. Imagine if the new genetically engineered organism evolves a little or exchanges genes with other ones. It could infect people, livestock, humans, bees, etc.
    When will people ever learn? There are natural measures to deal with mosquitos that don’t involve corrupting the DNA of life on earth.

  7. Tom

    So you got a mosquito that spreads malaria. And you got a fungus that is parasitic to this mosquito thereby killing it. But not fast enough… OK it is way cool that Fang can make the fungus do what he makes it do.
    However some fungi seem to exhibit an intelligence with communication…. I have experienced this myself with a pile of green mold, iridescent green, all shiny. But this pile of mold has its fungal state too. Existing simultaneously together. The mold can “travel” anywhere that the fungus has its “branches” (sorry I dont know what the term is). FAST. Travel fast…

  8. Tom

    …it seemed the mold could travel instantaneously from one place to another. I can tell you this too…they do not like plastic as found in plastic bags. The mold/fungus can be parasitic to humans, spreading rapidly along lymph lines, creating fistulas which pump hard white seeds eggs almost. Heres the word…grains like grains of sand. Totally painless. Self limiting. Scary. Think about a fiber optic cable…one section of that pile of mold can instantly be somewhere else via the fungal state. The mold can communicate its need/desire to the fungus..all the way up until you got fungus grains pumping from your arm.

    Where I am going is Fungi may not be good to mess with.

  9. This is also finding of green revolution

  10. RRH

    I thought it was interesting how fungus can act as weapon to stop the transmission of malaria. It’s amazing how more than 90% of the malarial mosquitos were killed when fungi was sprayed on surfaces.

    I sent the video to you because I think that rotting and molding fruits look beautiful. Just kidding, but I really do think they look cool. If you could, please explain to me why strawberries get fuzzy when they mold. (like this:
    It also relates to fungi~~!!!


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