Engineering fatter mosquitoes to fight disease

There’s been some promising news in the fight against mosquito borne diseases - such as dengue, Zika and yellow fever. A study at the university of Exeter has found that one particular bacterium, which lives in the insect’s intestine, can fuel the growth of mosquito larvae, so they mature much faster and may even grow into bigger adults. Why on Earth would you want to make more and fatter mosquitoes, I hear you scream! Well it could have implications for improving the breeding programmes used to rear modified mosquitoes designed to control wild mosquito populations and therefore disease spread. Here’s Ben Raymond at the University of Exeter…

Ben - The problem I wanted to address was really how to grow more and better mosquitoes for use in biological controlled studies of mosquitoes.

Chris - I'm glad you added that last bit because when you first said, I'm trying to find out how to grow more mosquitoes <laugh>, immediately I thought most of the world is trying to get rid of the blinking things. There are thousands of species of them and they are the most dangerous animal on Earth.

Ben - Yes, as I tell my students in many introductory lectures there's a higher mortality from mosquitoes than any other animal on the planet. For context, it's important to realise that releasing mosquitoes in various ways is now an increasingly important part of how we control mosquito-borne diseases. And there's a whole range of technologies that do that, ranging from classic sterile insect release, so that's just releasing lots and lots of sterilised males which swamp the native population of males that carry particular microbes. There's one in particular, Wolbachia, that induces sterility in the females but can also prevent those female mosquitoes from transmitting viruses. So there's a whole raft of technologies involved in releasing the particular strains to control mosquito populations.

Chris - But it all centres critically on being able to produce enormous numbers of mosquitoes. And that is the issue that you are kind of going for.

Ben - Yeah, so for example, there's a recent trial in Singapore. They released a hundred million mosquitoes just for an experimental study, another study releasing these Wolbachia to prevent transmission. They would release a hundred thousand mosquitoes per kilometre squared per week for 16 weeks. So really very, very large numbers.

Chris - What can you do then in order to make that a more efficient and rapid production process to breed up those mosquitoes that you want to release?

Ben - A starting point for this study was we're working with this particular mosquito, the yellow fever mosquito. And it's been known for a number of years that this has to be colonised by bacteria. It has to have what we call a microbiome in order to complete its development. Without being colonised by microbes, the larva will not develop and will not form a pupae and it can't produce adults. So we know it needs to have bacteria. And it did raise the question as to, you know, we can actually control what bacteria are colonising the mosquitoes and try and find ones that either can accelerate development or make bigger or better mosquitoes. So that's the starting point.

Chris - What have you actually done in that direction?

Ben - So we wanted to look at this little odd microbe Asaia, which is found in nectar. And we know from studies and other mosquitoes that it has strong association with mosquitoes that transmit malaria, the genus anopheles. So we wanted to look particularly in this yellow fever mosquito to see if they also could form an association with mosquitoes and would have any impact on their development.

Chris - How?

Ben - For these mosquitoes, it's quite easy to make sterile insects. You just need to sort of surface sterilise the eggs and then we can rear them in sterile water. We can then add in our bacteria of choice.

Chris - And what sort of a difference do they make when these ones you've found are there? How different is the maturation process for the mosquitoes?

Ben - So it only takes about nine days to make an adult from egg to pupa. So quite rapid development. So we could shave nearly a day off by adding one of the species of Asaia that we put into the rearing water. And in particular we showed that when we added our Asaia to the sterile animals, we didn't get much of an improvement. We got a little bit of improvement, but actually we could find nice robust effects on the sort of normal rear of mosquitoes, which is kind of important if you want to take this into an application.

Chris - So in other words, they're better when they're part of a community, a mixed community of microbes, they add something. Do you know how they're doing this? What are the bacteria in the mosquito gut doing to speed up growth in that way?

Ben - The bacteria in the gut have to make an environment that's starved of oxygen, so they have to remove the oxygen from the gut and that lack of oxygen drives the hormonal changes which signal moulting for the larvae. So that's one thing we know the bacteria are absolutely required for. We don't know if there's any sort of nutritional role these bacteria play. What the Asaia do is they don't seem to persist very long in the larvae. It's quite a curious result. But what they do do is have a long-term effect on the makeup of that bacterial community for the duration of the larval stage.

Chris - How would you use this then? If you can shave off a day, that's 10% off of the rearing cycle, does that mean that you could knock out lab grown mosquitoes about 10% faster and in possibly therefore 10% greater quantities?

Ben - That was one possible implication. The other thing we've looked at is we can also in some cases make the mosquitoes slightly bigger as well. So we're not only making them faster, but in some cases we can make them larger males and sometimes slightly larger females and get that boost in development rate. So hopefully more than one benefit.