Preventing the spread of malaria by anopheline mosquitoes can be done in two ways: completely eradicating all anopheles mosquitoes, which is next to impossible and would have environmental repercussions, or making them ineffective vectors. As previously discussed, by decreasing the likelihood for anopheline mosquitoes to harbor and transmit plasmodium, the parasite that causes malaria, rates of human malaria cases will decrease. This can be done many ways, but one method that researchers are investigating is not how to change the mosquitoes themselves, but how to change the bacteria in their bodies.

After a mosquito takes a blood meal, “[m]idgut bacterial populations increase 100- to 1000-fold,” so if scientists were to insert a GM bacterium that combats malaria into mosquito midguts, it should also replicate after a blood meal. At first, the researchers modified e. coli bacteria, but the lab e. coli didn’t survive in the mosquitoes, so they instead chose to use AS1, a bacterium that multiplies in mosquito ovaries, and engineer it to produce antimalarial proteins. AS1 had negligible effects on fitness and feeding behavior for both A. gambaie or A. stephensi mosquitoes, both before and after being edited to fight malaria. To make the bacterium counter plasmodium survival in host mosquitoes, researchers used a combination of different anti-plasmodium proteins with varying killing mechanisms to prevent the parasite from developing resistance. The mosquitoes infected with the GM bacteria with several antimalarial effector molecules had 92% less plasmodium oocysts, which means that the bacteria was immensely successful at preventing the growth of the malaria parasite in the infected mosquitoes.

Along with anti-plasmodium factors, the researchers gave the bacteria a gene that codes for eGFP or mCherry, which both produce a fluorescent protein that researchers could use ro keep track of the ASI bacteria inside the mosquitoes. The AS1-GFP bacteria were fed to mosquitoes in a sugar meal and managed to survive and reproduced despite the already existing microbiome, and its “numbers increased by more than 200-fold 24 hours after a blood meal.” AS1-GFP not only survived in adult mosquitoes, but could also be spread vertically and horizontally, meaning that offspring or mates of mosquitoes with AS1-GFP were also colonized by the bacteria. When males infected with the GM bacteria were mated with wt females, the AS1-GFP bacteria was found in the female mosquitoes, and in infected female mosquitoes, AS1-GFP clung to laid eggs, multiplied in the water, and were then eaten by the hatched larvae.

To test the longevity and infectiousness of AS1-GFP and ASI-mCherry, researchers set up a cage with 95% wt mosquitoes and 5% virgin female and male mosquitoes fed with the GM bacteria, and found that all the offspring of the infected mosquitoes carried the GM bacteria and continued to pass it on for the following generations.

Although the integration of the ASI bacteria was a huge success for the fight against malaria, finding ways to work it into wild populations remains a priority. In the next few weeks, expect to learn about how scientists plan to spread GM aspects into wild mosquito populations to curb the spread of malaria.

This was one of the first articles I’d heard about regarding the use of genetic modification to reduce malaria transmission, and it was the most easy to digest so far. It’s incredible how many different methods are being investigated to tackle this problem, and I really hope that we’ll start to see the impact of their implementation in the near future.

The past few days have been rough, so thank you to the like four of you that read these articles. It’s nice knowing that I’m not writing to the void anymore. Stay tuned to learn with me!

https://www.science.org/doi/10.1126/science.aan5478