Abstract
Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control.
Highlights
Malaria represents an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding
When mosquitoes ingest the gametocytes of the malaria parasite, Plasmodium with blood, they enter into the midgut and differentiate into gametes
We previously reported that the transmission of malaria to hosts was markedly reduced in transgenic mosquitoes expressing a single-chain antibody to the malaria circumsporozoite protein [6]
Summary
Malaria represents an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Insecticide resistance has recently been reported in mosquitoes in endemic areas, and, new strategies to control mosquitoes are expected [1]. Population replacement with genetically engineered mosquitoes to block malaria transmission is anticipated to become a new vector control strategy [2,3]. They traverse the peritrophic matrix and midgut epithelium, and differentiate into oocysts on the basal lamina. The sporozoites released in the hemolymph invade the salivary glands only. They remain in this tissue until the opportunity for blood feeding [4,5]. The salivary gland is an effective target tissue for the expression of molecules that kill or inactivate malaria parasites using transgenic technologies. We previously reported that the transmission of malaria to hosts was markedly reduced in transgenic mosquitoes expressing a single-chain antibody (scFv) to the malaria circumsporozoite protein [6]
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