BacterioFiles 320 - Fortified Fungi Fight Fevers

Anopheles gambiae

This episode: Fungi modified to produce spider and scorpion toxins kill malaria-transmitting mosquitoes extra fast!

Thanks to Brian Lovett for his contribution.

Download Episode (7.8 MB, 8.5 minutes)

Show notes:
Microbe of the episode: Microbispora parva

News item

Journal Paper:
Bilgo E, Lovett B, Fang W, Bende N, King GF, Diabate A, Leger RJS. 2017. Improved efficacy of an arthropod toxin expressing fungus against insecticide-resistant malaria-vector mosquitoes. Sci Rep 7:3433.

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Episode outline:

• Background: Statement 1
• This is Brian Lovett, one of two lead authors on today’s study.
• Statement 2
• These technologies could include Wolbachia and such, but takes time/effort and not universal
• What’s new: Now, Brian Lovett with other lead author Etienne Bilgo and also Weiguo Fang, Niraj Bende, Glenn King, Abdoulaye Diabate, and Raymond St. Leger, publishing in Scientific Reports, have developed an interesting way of controlling malaria mosquito populations: using modified fungi!
• Methods: Mosquitoes are Anopheles gambiae
• Transmit human malaria parasites
• Fungus is Metarhizium pingshaense
• Infects insects and kills them
• Modified here to produce neuron-targeting scorpion or spider toxins to further attack victims
• Also put in genetic control so toxins only produced when inside target insect
• Compared pesticide effectiveness of fungus with GFP or with various toxins
• Each toxin improved time to death by comparison similarly
• Pair even better, as Brian describes: statement 3
• Then exposed 3 types of mosquito (2 wild, resistant; 1 lab, susceptible to insecticides)
• Sheets with fungal spores, wild-type or with toxin
• Mosquitoes picked up enough spores for fungus to kill them regardless
• But with toxin, died ~2 days faster, 4 vs 6 total
• Statement 4
• Not good to spread insecticides indiscriminately though
• Could kill important good insects, like bees
• Tested fungus with or without toxins against bees
• But even when spores sprayed onto bees directly, no harm to bees
• Host specificity
• Summary: Mosquito-killing fungus even more effective when engineered to produce insect nerve-targeting toxins, and it’s good enough to consider for control of malaria and other diseases
• Applications and implications: Fungus + toxin meets WHO criteria for vector control agent
• Toxins EPA-approved too
• Statement 5
• Not too hard to deliver: just hang sheets with spores around house
• mosquitoes will land and pick up spores
• What do I think: Likely to evolve resistance?
• Fungus could also evolve
• But might not stick around enough for that
• Question of whether toxin benefits fungus
• If not, less likely to be maintained
• Probably harder to evolve strong resistance to both fungal pathogen and toxin at once
• Overall it could be very useful

Transcript:
1
Mosquitoes are the most deadly animals on the planet. Throughout history, and still today, the Grim Reaper too often arrives on the buzzing wings of a mosquito.

2
Throughout the US, many consider the mosquito to only be an annoyance. But US mosquitoes can and do transmit life-threatening pathogens. Pathogens, like Dengue virus, and the Aedes aegypti mosquitoes that best carry them, are already working their way up through our Southern states. The heaviest mosquito burden is felt in sub-Saharan Africa, where Anopheles mosquitoes deliver the malaria parasite, which cripples communities and kills mostly young children. Chemical insecticides, sprayed in houses or applied to bed nets, have allowed tremendous progress in malaria prevention, but resistance to these insecticides is rapidly spreading. To maintain and continue our progress against malaria, we need new technologies that can be integrated to manage both mosquitoes and insecticide resistance.

3
We showed that these fungi were capable of killing mosquitoes at a dose of one spore per mosquito. Three spores of a strain simultaneously expressing a spider and a scorpion toxin killed mosquitoes faster than either toxin alone.

4
And we also found that toxins caused mosquitoes to lose interest in blood feeding earlier and to a greater extent than a fungus without these toxins. Together, this means that our fungus strains are capable of preventing transmission of disease by over 90% of mosquitoes in just 5 days.

5
This study directly extends our understanding of how these technologies and toxins may be used in the field against mosquito pests and how mosquito biology may be exploited beyond simply killing the mosquito. We will use these results to further develop our efforts to apply transgenic fungi in the field, to prevent the spread of malaria. These findings will inform our ongoing NIH-funded studies testing the efficacy of transgenic fungi to control mosquitoes in Burkina Faso in Africa.