Researchers have chanced upon a bacteria naturally present in the gut of mosquitoes that inhibits the growth of a parasite that causes the deadliest form of malaria. Unlikely to produce resistance, the bacteria could be easily introduced in the field to complement existing malaria eradication strategies.
The mosquito-borne disease malaria is caused by five protozoan parasites, with Plasmodium falciparum being the deadliest among them, and the most prevalent on the African continent. Unlike its protozoan relatives, P. falciparum infects all types of red blood cells, from immature young cells to old ones. Left untreated, P. falciparum malaria can progress to severe illness and death within 24 hours.
The impact of malaria is well recognized, but little progress has been made in reducing deaths from the disease. According to the latest report from the World Health Organization (WHO), there were 249 million malaria cases in 2022 compared to 244 million in 2021. Now, researchers have chanced upon a bacterium that prevents the P. falciparum parasite from developing in the malaria-spreading female mosquito.
While studying a colony of mosquitoes as part of research into new drug development for GlaxoSmithKline (GSK), the researchers noticed that they were becoming increasingly difficult to infect with P. falciparum. Looking more closely at the mosquitoes and their breeding environments, they found that the insects carried a symbiotic bacterial strain called Delftia tsuruhatensis TC1, which slowed the growth of the protozoa in the mosquito’s gut, where it normally develops before moving into the salivary glands.
To investigate the potential for blocking the transmission of malaria parasites in other mosquitoes, the researchers performed lab experiments, giving D. tsuruhatensis TC1 to female mosquitoes followed by a Plasmodium-infected blood meal. Usually seen in the gut in small numbers, the number of D. tsuruhatensis TC1 increased about 100-fold following the blood meal and was seen in all mosquitoes. Once ingested, P. falciparum inhibited 73% of oocyst formation, stopping development for at least 16 days after colonization and possibly for the mosquito's life. Only 33% of mice were infected when bitten by mosquitoes carrying the bacteria.
The presence of D. tsuruhatensis TC1 didn’t affect the insect’s longevity, and they still produced the same number of eggs. Nor did it significantly affect their blood feeding rate. Bacteria were not released into the feeder when D. tsuruhatensis TC1-infected mosquitoes took a blood meal, suggesting that D. tsuruhatensis TC1 can’t be transmitted to humans through a bite.
Molecular analysis showed that the bacterium’s effects were due to the production of an active molecule called harmane, which, the researchers discovered, can be absorbed through the insect’s external surface (cuticle) and through digestion.
Field studies carried out in Burkina Faso, West Africa, showed that mosquitoes that acquired the bacteria from the field were as – or more – efficiently colonized by D. tsuruhatensis TC1 as lab-reared mosquitoes. The field studies, combined with mathematical modeling, show that D. tsuruhatensis TC1 has the potential to be used in conjunction with existing strategies to improve malaria eradication efforts.
Further, because the bacterium is not genetically modified and is part of the normal microbiota of mosquitoes, the insects are unlikely to develop resistance to it.
“The identification of a bacteria that prevents the development of the parasite stages that occur in mosquitoes without affecting them provides a novel approach with very little chance of developing resistance since it is not detrimental to the mosquitoes,” said Alfonso Mendoza-Losana, one of the study’s co-authors. “In addition, it is a non-genetically modified bacteria, which allows for rapid introduction in the field.”
The study was published in the journal Science.
Source: UC3M