New Genetic Approaches to Reduce Malaria Transmission by Mosquitoes

Highlights:

• The introduction of modified bacteria or improving immunity in mosquitoes can reduce malaria transmission
• The modified bacteria inhibit the growth of the malarial parasite and are passed on through successive generations
• The improved immunity due to genetic modification changes the bacterial flora in the mosquitoes as well as their sexual preferences, thus allowing the modification to pass on through generations

Two genetic approaches that target mosquitoes and their microbiota could help to reduce transmission of malaria in endemic regions. The studies that evaluated these approaches were published in Science. In the first approach, the scientists fed mosquitoes with a modified bacterium called Serratia AS1 in a sugar meal. The bacterium was modified to produce five anti-Plasmodium effector proteins, which inhibit the development of the falciparum malaria parasite in the gut. Thus, in this approach, there were no direct changes introduced in the genetic constitution of the mosquito. The scientists found that:

• The modified bacterium remained in the gut and inhibited the development of the malaria parasite in the digestive tract. When the scientists integrated it with a gene coding for a fluorescent protein and fed it to the mosquitoes along with a sugar meal, they found that it efficiently populated the digestive tract and its numbers increased more than 200 times 24 hours after the mosquito had a blood meal.
• The bacterium colonized the accessory glands of the male mosquito and was easily transmitted sexually from the male to the female mosquito. When the infected males were allowed to mate with virgin female mosquitoes, the fluorescent-tagged bacteria were transmitted to the females and were found in their gut and ovaries.
• Since the bacterium colonized the ovaries, it spread easily through generations. The number of infected mosquitoes increased from 5% to 100% in a single generation. The infection was maintained in the subsequent generations that were studied.
• The bacterium did not affect the life span, blood-feeding behavior or fertility of the mosquitoes.

In the second study, the mosquitoes were genetically modified to increase their immunity and make them more resistant to infection with the malarial parasite. The scientists found that:

• The genetically-modified mosquitoes showed a preference to mate with non-modified mosquitoes of the opposite sex. The modified males preferred normal females, while the normal males preferred modified females. When equal numbers of modified and non-modified mosquitoes were kept together, around 90% of the mosquitoes were genetically modified in the first generation and the number as well as the resistance to the malarial parasite was maintained through 10 generations.
• The change in the immune status changed the type of bacteria in the gut of the mosquitoes, which was responsible for the change in their sexual preferences. Killing the bacteria using antibiotics temporarily eliminated the preference, which proved that the altered bacterial status determined the sexual preference.
• The modification of the mosquitoes did not affect their longevity, the number of eggs laid or the sex ratio in the offspring. The resistance to the malarial parasitic infection due to the modification lasted for several generations.

The new approaches ensure that the mosquitoes that have undergone the changes show resistance to the bacteria, and in addition, the resistance persists and spreads to subsequent generations. Further development of these approaches could reduce dependence on current preventive measures like insecticides.

About Malaria

Malaria is a common tropical disease caused by the Plasmodium parasite and spread through the bite of the female Anopheles mosquito. Though antimalarial medications are available, the parasite sometimes develops resistance, which makes it difficult to treat. Falciparum malaria can take a life-threatening course, while vivax malaria is characterized by relapses if not treated adequately. Prevention of mosquito bites using repellents and mosquito nets, and preventing the breeding of mosquitoes are measures that can control the infection to some extent. Unfortunately, even mosquitoes are developing resistance to insecticides, which requires the urgent development of alternative methods. 

References:

1. Wang S et al. Driving mosquito refractoriness to the malaria parasite with engineered symbiotic bacteria.
2. Pike A et al. Changes in the microbiota cause genetically modified Anopheles to spread in a population.

Source-Medindia