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Yeast symbionts of malaria vectors: from basic research to the management of malaria control

Final Report Summary - SYMBIOVEC (Yeast symbionts of malaria vectors: from basic research to the management of malaria control)

Yeasts are single-celled microorganisms that are classified, along with molds and mushrooms, as members of the Kingdom Fungi. Some yeasts can interact with other species. In fact, they can be dependent on another organism for survival, and benefit the host. When two species live close together and form a stable relationship, it is called symbiosis. Many insects have a symbiotic relationship with certain types of yeasts. Several examples have shown the ability of the insect to survive on a diet based on yeast consumption only. Moreover, yeasts have shown the ability of suppressing pathogens that might hamper the development of the insects. For the yeasts, the main benefit of the mutualism is the enablement of processes such as outbreeding and spreading offered by contact with insects.
Understanding the key elements and functions in yeast-insect interactions could lead to the development of better pest management. As regards the arthropod-borne diseases, a particular attention should be focused on the prevention of mosquito-borne diseases such as malaria that kills millions of people each year, making this insect the world’s deadliest animal.
An efficient vaccine against malaria is not yet available and the current control methods, mostly represented by drugs and insecticides, are becoming less and less effective. Consequently, the malaria burden is increasing in some sub-tropical regions, and its global projection could show a spreading in the next decades.
The Symbiotic Control (SC) is a new and alternative strategy to prevent malaria (or other insect-borne diseases) through the use of microbial symbionts of the insect-vector. The symbionts can be used as a Trojan horse to deliver substances able to kill the pathogens in the mosquito gut, blocking the transmission of infections to humans. Interestingly, this approach does not eliminate the mosquitoes (like an insecticide) but it makes them refractory to malaria. This strategy prevents the emergence of selected mosquitoes resistant to chemicals that is one of the main problem with the use of insecticides.
The breakthrough of the project was the identification of a yeast symbiont (Wickerhamomyces anomalus AS.F17.12) in the mosquito gut and gonads. Wa-AS.F17.12 is horizontally transmitted among mosquitoes during feeding and mating, and it is inherited by the offspring. The yeast spreading mechanisms were studied both in the laboratory and in semi-field conditions. The latter experimentation was an essential step from the bench to the field.
Notably, Wa-AS.F17.12 exerts a wide antimicrobial activity through a Killer Toxin (KT) that kills several microbes, such as fungi, and protozoa including the malaria parasite. KT is not dangerous for humans and the environment, because it targets specific microbial structures.
The SymbioVec research results indicated that, Wa-AS.F17.12 is an ideal candidate for SC applications as it (i) shows a natural killer phenotype against the malaria parasite; (ii) is not pathogenic; (iii) is environmentally friendly; and, is active against other pathogens, being potentially applicable to other vector-borne diseases. Additional characteristics are that it (iv) is easily cultivable; and, (v) is stable at different temperatures and pH values, with a remarkable survival during storage. These features are essential for using a microorganism on a large scale, since this requires the microbial formulation and stabilisation.
Taking into account all these aspects, Wa-AS.F17.12 is proposed as an innovative product to prevent malaria. Practically, a yeast-based biocide can be released in the environment through a spray formulation in the mosquito breeding and feeding sites. The mosquitoes ingest the yeast that in the gut of the vector kills the malaria parasite, before it is transmitted to humans.
An advantage of using a biocide is that it is an ‘alive’ compound, hence it can self-spread in the mosquito populations by horizontal and vertical transmission routes. This opportunity reduces the cost of multiple interventions and does not impact the environmental health like the insecticides.
Formulations containing killer yeasts can be introduced cheaply, easily, and safely in the endemic regions, supporting the existing malaria control systems. Next step is the involvement of small-medium enterprises for the production and the commercialisation of this product.