Will mosquito vectors evolve resistance to an emerging bacterial biocontrol agent?

Scientists examine how mosquitoes are likely to evolve in response to biocontrol agent being used to reduce transmission of viruses like dengue, chikungunya and Zika to humans
Will mosquito vectors evolve resistance to an emerging bacterial biocontrol agent?

Wolbachia pipientis is a bacterium that lives inside the cells of ~50% of insects. Transmitted from mother to offspring, the bacterium spreads through insect populations by improving the reproductive success of females. Wolbachia also prevents viruses from replicating inside insects. Together, these characteristics have made Wolbachia attractive to biocontrol researchers – dreaming of using Wolbachia to stop mosquitoes from transmitting viruses to humans.

Aedes aegypti is a mosquito that transmits several dangerous viruses to humans including dengue, Zika, chikungunya and yellow fever. Often called the cockroach of mosquitoes, it thrives in urban environments. This mosquito species is naturally free of Wolbachia, however, and so the bacterium first had to be transferred from another insect before it could be used for disease control in the mosquito.

Multiple research teams are releasing Wolbachia in the tropics where transmission of mosquito-borne viruses is most common. Early evidence from these field-trials shows that Wolbachia is able to reduce the local incidence of dengue fever in humans. One concern with the long-term efficacy of Wolbachia is whether the mosquito or virus will evolve resistance to the agent. Because we do not understand the mechanism by which Wolbachia ‘blocks’ virus replication it is difficult to predict if, when, or how resistance might arise in the mosquito.

Here, we performed an evolution experiment in real-time in the laboratory. Specifically, we artificially selected for Wolbachia-infected mosquitoes that exhibited either better or worse dengue virus blocking. We then asked which of these mosquitoes grew the fastest. Any differences might tell us how quickly resistance could evolve and in what direction. We also examined the location of any genetic variation in the mosquito and Wolbachia genomes that gave rise to changes in virus blocking ability. Knowing the key genes could shine a light on how Wolbachia was limiting viral replication.

We found that blocking responded to selection, meaning that there was genetic variation for this trait. We then discovered that the mosquitoes with better viral blocking also had a faster growth rate- a trait that would benefit the spread of strong blockers. Consistent with this, we found that strong blocking was already common in our unevolved population and therefore difficult to improve upon. Despite this, we still found plenty of genetic variation in the population for evolving poor blockers. The’ glass is half-full’ interpretation is that this association between mosquito growth rate and blocking should avoid the loss of blocking in the wild. The ‘glass is half-empty’ interpretation is that it was easy to lose blocking in the laboratory, and that in the field where environmental conditions are different and more complex this could also occur. 

We also showed that Wolbachia may limit viral replication through cell adhesion in the mosquito, potentially limiting the viruses’ ability to enter and move between mosquito cells.  These represent key stages of the virus lifecycle, as the virus makes its way from the point of blood meal ingestion in the mosquito gut to its saliva, which is injected into a human on a subsequent bite. 

Poster image design by Marli O'Neill