Gut bacteria from Aedes aegypti could be weapon against dengue and other diseases

During the São Paulo School of Advanced Science in Arbovirology, researchers presented findings showing that infection of mosquitoes by pathogens can be blocked, interrupting transmission to humans.

By Karina Toledo  |  Agência FAPESP – Like humans, mosquitoes have guts that are home to an enormous variety of bacteria. Recent studies suggest that modulating mosquitoes’ gut microbiota profile could be an effective strategy to make them more resistant to infection by pathogens. This would be an alternative method of controlling the spread of diseases such as dengue, Zika, yellow fever, chikungunya and malaria, among others.

The subject was addressed by George Dimopoulos, a professor at Johns Hopkins Bloomberg School of Public Health (USA), during the São Paulo School of Advanced Science in Arbovirology. Supported by FAPESP, the event took place between May 29 and June 9 in São José do Rio Preto, São Paulo State, Brazil.

“Until now, vector-borne diseases, especially dengue, have been combated basically by the application of insecticides and environmental modifications such as eliminating the breeding-grounds of the mosquitoes responsible for transmission. Although these methods have achieved some success, there are logistical difficulties with maintaining them in the long term and setbacks are therefore frequent. New control strategies need to be developed,” Dimopoulos told Agência FAPESP.

In his laboratory, Dimopoulos fed mosquitoes of the species Aedes aegypti (which transmits dengue, Zika, yellow fever and chikungunya viruses) and Anopheles gambiae (which transmits malaria parasites) on an artificial nectar that colonized their guts with bacteria of the genus Chromobacterium.

The experiment showed that the bacteria drastically reduced the survival of both larvae and adult mosquitoes. Moreover, the survivors became less susceptible to infection by dengue virus in the case ofAedes aegypti and by Plasmodium falciparum in the case of Anopheles gambiae.

“The idea would be to develop a biopesticide made from these bacteria, which are naturally found in soil and inoffensive to human health,” Dimopoulos said. “We could spray it in the environment like an insecticide or exploit the insects’ preference for sugar by creating an artificial nectar that could be placed in devices to attract mosquitoes. It would also be possible to use these same bacteria to create pellets that could be placed in breeding-grounds to affect the larvae.”

In his presentation, Dimopoulos said that other approaches using bacteria of the genus Wolbachia are also being tested for applications to control dengue in various parts of the world, including Brazil.

“Studies have shown that when certain strains of this microorganism are present in the gut microbiota of Aedes, they make the mosquito resistant to infection by both dengue and Zika,” he explained. “This bacterium is transmitted by the mother to its offspring, so it could be propagated automatically to an entire population of mosquitoes.”

According to Dimopoulos, in theory, it would suffice to release a small number of mosquitoes infected with the key strain of Wolbachia. They would mate with wild mosquitoes and transmit the bacterium to their offspring, which in turn would transmit the bacterium to the next generation, and a large proportion of these insects would gradually become resistant to the pathogen.

“One thing is certain: we need many different strategies to control these vector-borne diseases: drugs, vaccines, mosquito control, and also perhaps some of these newer strategies that block infection in the insects. It’s like fighting a war. You cannot win a war using one weapon only,” Dimopoulos said.

Geographic influence

Also during the São Paulo School of Advanced Science in Arbovirology, Jayme Augusto de Souza-Neto, a researcher affiliated with São Paulo State University (UNESP) at Botucatu (São Paulo State, Brazil), presented the latest results of his line of research, which compares the microbiotas and genetic profiles of three different populations of Aedes aegypti mosquitoes.

The specimens were collected in three cities: Botucatu, Neópolis (Sergipe) and Campo Grande (Mato Grosso do Sul). After feeding the mosquitoes in the laboratory using blood contaminated with dengue virus serotype 4, the group found that only 30% of the mosquitoes collected in Botucatu had been contaminated, compared with 70-80% for the other two samples, which came from places with a higher incidence of dengue.

Using large-scale gene sequencing techniques, the group identified the species of bacteria that colonized the mosquitoes’ guts and found that the more susceptible and less susceptible groups had completely different gut microbiomes.

The data also showed that whereas in the mosquitoes from Botucatu the infection made very little difference to gene expression, in the other populations, several genes were activated or suppressed in response to the virus.

“At first we thought the difference observed in the microbiome could have been caused by the immune response triggered by the virus, but when we assembled several populations in a more complex analysis we found that the results were grouped not by susceptibility to infection but rather in terms of the site at which the mosquitoes were collected,” Souza-Neto said. “This suggests the microbiome was defined by geography.”

The hypothesis on which the UNESP group is now working is that the microbiota of Aedes is genetically defined. These two factors together – genome and microbiota – may determine whether the insect will be infected by dengue virus. The research was supported by FAPESP, and according to Souza-Neto, the results could lead to novel strategies for controlling the disease (read more at: agencia.fapesp.br/21178/).