Malaria: Bacterium found in mosquito gut could boost fight against disease

Water, sugar and a little something extra

Malaria: Bacterium found in mosquito gut could boost fight against disease

Water, sugar and a little something extra. This could become the new weapon to complete the arsenal of the fight against malaria. A disease that affected in 2021, according to the latest figures available from the World Health Organization (WHO), 247 million people worldwide, including 95% on the African continent, and killed 619,000 people.

That little something extra has an extended name: Delftia tsuruhatensis TC1. Discovered by a team of Spanish, British, Burkinabé and American researchers from the Johns-Hopkins-Bloomberg School of Public Health in Baltimore, United States, and from the British laboratory GSK, this bacterium has the property of preventing the development at a very early stage of the Plasmodium falciparum parasite, responsible for malaria, in the digestive tract of mosquitoes.

The results of their research were published in the journal Science on August 3. "It was our researchers at the Tres Cantos (TC) site in Spain who made the discovery," says Janneth Rodrigues, chief scientist at GSK, co-author of the study. It was found that the colony of mosquitoes in our insectarium was no longer able to maintain infection with P. falciparum, the most widespread and deadliest type of malaria, particularly in Africa. Some had a much lower Plasmodium load (up to -75%), explains the study.


The researchers wondered why and it was in the microbiota of the female mosquito that they found the answer. "D. tsuruhatensis was found to be predominant in all samples examined, continues the researcher, and the Tres Cantos 1 (TC1) strain was identified as responsible for the loss of infectivity. »

Better, they spotted that the bacterium D. tsuruhatensis TC1 produces a small toxic molecule called harmane, well known to scientists, which acts as a sentinel by inhibiting the development of the parasite in the digestive tract of the mosquito.

The harmane acts after the mosquito has ingested the bacteria, but it also has the property of passing through the "skin" and the skeleton of the insect (the cuticle in scholarly language). This opens up a second perspective, that of making it a contact product, which one could imagine being able to spray on mosquito nets for example.

If the researchers have not yet completely deciphered how the toxin manages to stop the growth of P. falciparum, "it is a major discovery, one of those which could tip the fight towards eradication", estimates Pierre Buffet, director of Institut Pasteur, clinician in infectious dermatology and tropical medicine: "It's exciting, original as a research angle. We are there in the field of biological control which raises real hopes while the fight against the disease is stagnating. »

cotton balls

There is still a long way to go before we can market a harmane-based product or consider using the bacteria on a large scale, but the trials carried out in Burkina Faso are promising, the study explains. The climatic conditions of Anopheles proliferation were reproduced in a confined environment at the Muraz Center of the Institute for Research in Health Sciences (IRSS) in Bobo-Dioulasso, by providing the populations of mosquitoes studied with water and nutrients. they feed on as well as cotton balls soaked in water, sugar and D. tsuruhatensia TC1. It only took one night for the bacteria to colonize three-quarters of the mosquitoes.

The experiment continued by exposing a cohort of mice to mosquitoes carrying the rodent malaria parasite (P. berghei) and the bacterium and another cohort to mosquitoes carrying only P. berghei. The result is edifying: only a third of the animals exposed to mosquitoes infected with murine malaria and D. tsuruhatensis TC1 had been contaminated, while the second cohort was completely contaminated.

Finally, last promising point: the researchers demonstrated that the toxin not only inhibited the development of the pathogenic parasite for rodents (berghei), but also for humans (falciparum), whether in the laboratory or outdoors, which gives hope efficacy on the other four Plasmodium dangerous to humans: P. vivax, P. oval, P. malariae and P. knowlesi.

"Before considering large-scale use, this research must continue to find out if the bacterium and the toxin can have consequences on other organisms, such as pollinating insects for example, which would be catastrophic", explains Olivier Silvie, research director at Inserm and number two at the Center for Immunology and Infectious Diseases in Paris.

No transmission to eggs

Even if it has been demonstrated that the bacterium D. tsuruhatensis TC1 is pathogenic for humans only in an absolutely exceptional way, experimentation continues in Burkina Faso to ensure the safety of a product based on harmane, a neurotoxic alkaloid. "Our research shows that harmane plays its inhibitory role at very low concentrations, at nanomolecular levels," explains Janneth Rodrigues. Negligible amounts for human health. »

Harman is indeed naturally present in many plants, such as coffee for example, food, tissues and fluids of mammals and is also stored in organs such as the liver and the brain. “We successfully conducted preliminary studies in the “mosquito sphere” [insectarium] at the IRSS in Bobo-Dioulasso which showed that our laboratory results could be transposed to the field. This is what prompted us to undertake extensive studies in a semi-open environment that are currently underway. »

Another avenue of research remains to be explored, anticipates Pierre Buffet, of the Pasteur Institute: that of a genetic modification of the bacterium so that it becomes transmissible by the female Anopheles mosquito to its offspring, which is not the case in the natural state. “Because without transmission from females to their eggs, the mosquito will have to be constantly “fed” with the bacteria, explains the malaria specialist. This is not impossible to achieve, but it limits the durability of such a device. Not to mention the cost. Another hope for the eradication of malaria which will require removing doubts about the environmental consequences of the use of a GMO, and ethical resistance.