Research Article: Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells

Date Published: September 6, 2016

Publisher: Public Library of Science

Author(s): Daisuke S. Yamamoto, Megumi Sumitani, Katsumi Kasashima, Hideki Sezutsu, Hiroyuki Matsuoka, Rita Tewari.

http://doi.org/10.1371/journal.ppat.1005872

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.

Partial Text

Malaria represents an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective ways to control malaria in endemic areas. Insecticide resistance has recently been reported in mosquitoes in endemic areas, and, thus, 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].

In the present study, we produced transgenic An. stephensi containing distal-lateral lobe-aberrant salivary glands with extremely low amounts of salivary components. We found that oocyst formation in the midgut was markedly inhibited in this transgenic line. The homogenate of the salivary glands of this line suppressed exflagellation, which is an essential event in microgametogenesis before the fertilization of Plasmodium in the mosquito midgut. These results indicate that anopheline mosquito saliva plays an important role in blood feeding as well as in interactions with malaria parasites in the midgut. A previous study reported that the inhibition of the surface component of salivary glands, Saglin protein suppressed salivary gland invasion by sporozoites [11]. We herein demonstrated for the first time that the salivary glands are important for the transmission of malaria parasites to the midgut of mosquitoes.

 

Source:

http://doi.org/10.1371/journal.ppat.1005872

 

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