Last Updated: 02/09/2025
Symbiotic control of vector mosquitoes: from the laboratory to the field
Objectives
- Paratransgenic mosquito development with reduced or abolished ability to transmit malarial parasite.
- Paratransgenic mosquito release under semi-field conditions to determine its diffusion dynamics in recipient populations and in later generations.
The role of mosquitoes is of enormous importance, being responsible for the transmission of diseases such as malaria, dengue, yellow fever, Chikungunya, whose epidemiological frameworks reflect the inadequacy of current prevention measures. More effective strategies, based on vector control and aimed at interrupting the transmission of the pathogen, could reverse the trend of steady increase in entomogenous diseases. In addition to conventional control strategies, new biotechnology methods, already applied successfully in controlling some insects of economic interest, could also be developed and applied for the control of mosquito-transmitted diseases. In this context, the so-called “symbiotic control” is introduced, a new multiform approach that uses entomophilic microorganisms to interrupt the transmission of pathogens associated with vector insects.
In order to achieve the first objective, it is proposed to engineer mosquitoes of the Anopheles stephensi species (one of the major malaria vectors in Asia) to make them unable to transmit Plasmodium by the construction of a recombinant symbiote consisting of a bacterium of the genus Asaia, In particular of the A. bogorensis species (densely associated with the major malaria vectors), capable of expressing the surface WSP of Wolbachia sp. Wolbachia sp. is a bacterium of the Rickettsiaceae family that infects the reproductive organs of many species of mosquito but not those malaria vectors, belonging to the Anopheles only genus. The possibility that A. bogorensis-WSP recombinant symbionte can be used successfully in controlling malaria transmission is based on three main considerations:
i) Wolbachia sp. stimulates the innate immune response in mosquitoes by reducing the capacity of many pathogens. The use of Wolbachia sp. in paratransgenic applications is compromised by its inherent intracellular symbiotic characteristics, which makes it unsuitable for environmental release, and is not cultivable in the cell-free media. It has been shown that WSP is a powerful inducer of the innate immune response and in recombinant form increases the transcription of immune genes in Anopheline cells, naturally not infected with Wolbachia. WSP could therefore represent an effective molecule for paratransgenic control strategies.
ii) A. bogorensis is a gram negative acetic acid, cultivable and transformable, recently described by the Coordinator’s Research Unit (UR) as a commensal in many species of mosquito. Transformation and colonization experiments have shown that A. bogorensis recombinant strains are able to colonize the intestine, salivary glands and reproductive organs massively, posing as plausible paratransgenic control agents.
iii) In the field of mosquito-borne diseases, one of the greatest successes of recent years was that obtained in the “Wolbachia-mediated” suppression of the transmission of Dengue. The same criterion, however, cannot be applied to the control of malaria, as mosquito vectors are refractory to infection by Wolbachia sp., but the approach proposed could overcome this limit. An exit strategy is also foreseen in the case, unlikely, that A. bogorensis-WSP does not have an effective effect on the interruption of malaria transmission. Two other “interacting effector molecules” with the mosquito immune system are described today, making it refractory to infection by Plasmodium: Akt (an insulin signaling pathway component) and Rel2 (a transcription factor of the immune mosquito immune pathway IMD). These two molecules will be used to develop recombinant strains of A. bogorensis.
As regards the achievement of the second objective, the semi-field release of paratransgenic mosquitoes is an essential prerequisite for acquiring all the useful information about the dispersion dynamics of recombinant strains of Asaia, which is a key element for definitively clarifying the paratransgenic potential Before a possible release on the field.
Jan 2012 — Jan 2015
$660,000
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