Thread by @lovettbr

Hello Twitter friends! Our team had a paper come out describing years of work in the semi-field in Burkina Faso, and I want to talk about what we found and how this fungal biotechnology is developing. science.sciencemag.org/content/364/64…

First, let's describe the platform we're working with. I say platform because the technology we're working with is interchangeable.

In the study that was published today we used one particular strain of fungus that has specialized to kill mosquitoes, but we could engineer this same technology with a strain that is specialized to another insect, like locusts.

Here, we used a Blue Mountains funnel-web spider toxin called Hybrid, which is specific to two channels on insect neurons, but we could use any number of insect-specific toxins to engineer strains that target different sites and could be used together or rotated. (cc @VenomsLab)

Naturally, our fungal strain (Metarhizium pingshaense) does some amazing things. First, it can tell when it's on a mosquito by sensing the landscape of the cuticle and with chemical cues on the surface. If all signs point toward mosquito, alons y into the blood of the mosquito!

Once it's bathing in mosquito blood, the fungus has a problem. All sorts of alarm bells go off in a mosquito's immune system if large, filamentous fungal hyphae are in its blood. To avoid this, the fungus uses an "invisibility cloak" and grows as little yeast-like ovals.

This invisibility cloak is not magic, it's science! The fungus surrounds itself with a very animal protein, collagen. This, with the shape change, hides the fungus from the immune system. Importantly, the fungus only creates this invisibility cloak in the blood of insects.

This means we can use the on/off switch for this gene to express new genes, in this study a spider toxin, specifically in the blood of mosquitoes. Here we have a mosquito-selective fungus expressing an insect-specific toxin only when it's in mosquito blood.

Spiders use their fangs to deliver their insect-specific toxins into the inside of insects, and here, we are using the natural abilities of this fungus to do the same job!

The study in question is looking at whether or not this fungal biotechnology works as well in field conditions as it did in the lab. Since this is transgenic, we couldn't test it in the open field just yet, so we built an @NIAIDNews-funded facility called a MosquitoSphere.

This facility is like a large greenhouse with mosquito netting instead of glass. The MosquitoSphere has six compartments with four containing experimental huts surrounded by local vegetation and breeding sites, and the other two are for rearing mosquitoes and cattle.

Cattle provided blood for mosquitoes we reared from wild-caught larvae: ensuring they represent the insecticide-resistance and genetic diversity of the area. The facility is important because it allows environmental conditions in, but keeps our experiments inside.

So what did we discover in this contained facility? We found that in field conditions this fungal biotechnology kills mosquitoes more quickly and kills more mosquitoes than the wild-type fungus.

We also found that infection by this fungus causes female mosquitoes to lay fewer and poorer-quality eggs, which resulted in a collapse of established populations after two generations.

Finally, we showed that the effective persistence (the amount of time the treatment stays effective) is increased compared to the wild-type fungus in field conditions! This is because it only requires a few spores to kill a mosquito when they deliver a potent neurotoxin.

In previous studies, we've shown these transgenic fungi halt biting (required for transmission) before the mosquitoes die. nature.com/articles/s4159…

These fungi also work synergistically with pyrethroid insecticides: our primary defense against malaria mosquitoes. Applied with these chemical insecticides, we could manage insecticide-resistance to bring insecticides back on the table. journals.plos.org/plosone/articl…

These are promising scientific results, and it is due in large part to our incredible collaborators in Burkina Faso, particularly Dr. Abdoulaye Diabate and Dr. Etienne Bilgo @bilgo02, and the support of the community in Soumousso.

Science has an ally in Soumousso, as this Burkinabe village is also where insecticide treated bed-nets were first tested in field trials. They have a long history of supporting innovative science that has saved lives all over the world: we can't thank this community enough.

We are developing this technology to empower communities to have more options to control malaria mosquitoes and prevent this debilitating disease. Further development will require consultation with stakeholders at all levels to earn acceptance, and I'm looking forward to it.