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Discovery paves the way for barring malaria transmission in Brazil

Publicado em 22 novembro 2019

The bacteria that form the gut microbiota influence important processes in the human organism, such as digestion, nutrient absorption and defense against pathogens. The same kind of relationship is present in most animals, including the mosquito. Anopheles darlingi, the main vector of malaria in Brazil.

In the case of this insect, the composition of the intestinal microbiota appears to determine susceptibility to infection with Plasmodium vivax —Species responsible for 90% of malaria cases in Brazil. That is, when the mosquito bites a sick human, an interaction occurs between the parasite and the insect's intestinal bacteria that is crucial for the continuation of the disease transmission cycle.

This is the conclusion of a study conducted at Paulista State University (Unesp) that was presented on Friday (22) in Lyon, France, during the symposium Fapesp Week France. According to the researchers, the discovery allows us to think of strategies to block malaria transmission in the vector.

"We found that in the intestine of the Anopheles, the parasitic load influences the microbiota composition and vice versa. After investigating the parasite-bacterial relationship further, integrating microbiota composition data with genetic analysis regarding mosquito immunity, we intend to carry out gene silencing studies. The goal is to develop mosquitoes that are immune to Plasmodium vivax, meaning that they do not become infected and therefore do not transmit the parasite to humans, "said Jayme Augusto de Souza-Neto, professor at the Department of Bioprocesses and Biotechnology, School of Agronomical Sciences from Unesp de Botucatu and project coordinator supported by Fapesp.

Immune system is the key

This is the first study to analyze in an integrated way the transcriptome (the set of expressed genes) and the microbiology of Anopheles darlingi infected by Plasmodium vivax.

Previous work by another group of mosquito scientists Anopheles gambiae infected by protozoa of the species Plasmodium falciparum, had shown that the microbiota influences parasite development within the mosquito. When comparing insects with and without bacteria in the gut, it was found at the time that the microbiota as a whole interferes with protozoan development. It has been found that when there are no bacteria (when they are eliminated with antibiotics, for example), Plasmamodium tends to develop more easily in the insect vector organism.

The work carried out at Unesp goes on to demonstrate that not only the presence of bacteria in the gut, but, above all, the composition of this microbiota seem to be determinant in the intensity of the infection.

"In groups of mosquitoes with low parasite infection, we also observed a low amount of bacteria and a high immune response. In groups with high parasite infection, there was a high amount of bacteria and a low immune response," said Souza-Neto .

The researchers also compared the transcriptional responses (the gene expression profile), the charge and the composition of the gut microbiota. "There is a difference in microbiota composition between the groups of insects with high and low parasitic load. Probably, this is related to the immune response, which is also different in these two groups," he said.

The microbiota of the mosquitoes studied was basically composed of varied strains of two families of bacteria: Enterobacteriales and Flavobacteriales. "There is a dynamic. When the parasite load increases, some specific bacteria become more abundant and others less. It seems that they act in this process in a well coordinated manner," said the researcher.

According to Souza-Neto, as the immune response is shared between bacteria and parasite, defense against the parasite also affects bacteria and vice versa. "By observing this bacterial-parasite interaction we realize that, in general, bacterial and parasitic loads follow exactly the same trend. The explanation seems to be related to the expression profile of genes linked to the mosquito's immune system," he said.

"The transcriptome was associated with the complement system (proteins that are part of the invertebrate immune system) of the mosquito. Previous studies have linked the response against the parasite with the complement system. Our interest is to find genes that, when overexpressed, make the mosquito refractory. protozoan infection, so that it cannot also transmit the parasite to humans, "he said.

Another possible explanation would be the microbiota response to the parasite. "Bacteria produce proteins, metabolites, or molecules with antiparasitic action. It is possible that reactive oxygen species, such as hydrogen peroxide, can help kill the Plasmamodium and that this direct action occurs independently and simultaneously with the mosquito's immune system, "he said.

The discovery makes it possible to develop population modification strategies in the future, such as releasing transgenic mosquitoes immune to the malaria parasite in the wild. The approach is different from population suppression recently attempted to fight dengue, which is to release sterile males of the species. Aedes aegypti.

"This strategy would be especially interesting for Brazil, where the Anopheles darlingi is the main vector for malaria, but also for other South American countries, "said Souza-Neto.

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Time 24 News (EUA)