Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.
Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.
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DOI：
10.1371/journal.ppat.1005872
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发表时间：
2016-09
期刊：
影响因子：
6.7
通讯作者：
Matsuoka H
中科院分区：
文献类型：
--
作者：
Yamamoto DS;Sumitani M;Kasashima K;Sezutsu H;Matsuoka H
疟疾是一个重要的全球公共卫生挑战，由按蚊在吸血期间传播。蚊媒控制是控制疟疾最有效的方法之一，利用基因工程蚊子进行种群替换以阻断其传播有望成为一种新的蚊媒控制策略。唾液腺是表达杀死或消灭疟疾寄生虫的分子的有效靶组织。此外，唾液腺细胞表达大量分子，促进吸血和寄生虫传播到宿主。在本研究中，我们适应了特定组织中的功能缺陷系统，通过诱导细胞死亡，使用小鼠Bcl-2相关的X蛋白（Bax）的亚洲疟疾媒介蚊子，斯氏按蚊。我们将这种技术应用于唾液腺细胞，并产生了含有极少量唾液的转基因株。尽管转基因蚊子对老鼠的取食时间比野生型蚊子长，但转基因蚊子仍然成功地摄取了血液。转基因蚊子在啮齿动物疟疾模型中也表现出中肠卵囊形成的显著减少。这些结果表明，蚊唾液在按蚊中肠疟疾感染中起着重要作用。唾液腺功能障碍能够抑制疟疾从宿主传播到蚊子中肠。因此，唾液成分在开发用于疟疾控制的新药或基因工程蚊子方面具有潜力。由按蚊传播的疟疾是一个重要的全球公共卫生挑战。蚊子的唾液腺是疟疾和病媒控制的一个有吸引力的目标组织。我们在亚洲疟疾媒介蚊子斯氏按蚊中产生了一种诱导唾液腺细胞死亡的转基因菌株，该转基因菌株具有细胞死亡效应分子。这种转基因菌株含有极少量的唾液。对这种菌株的分析表明，唾液在啮齿动物疟疾模型中的中肠中的探测和疟疾感染中起着重要作用。唾液腺的功能障碍能够抑制疟疾向蚊子中肠的传播。因此，唾液成分在疟疾控制中也很重要。
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. Malaria, transmitted by anopheline mosquitoes, represents an important global public health challenge. The salivary glands of mosquitoes are an attractive target tissue for malaria and vector control. We produced a transgenic strain inducing cell death in the salivary glands with a cell death effector molecule in the Asian malaria vector mosquito, Anopheles stephensi. This transgenic strain contained extremely low amounts of saliva. An analysis of this strain revealed that saliva plays an important role in probing as well as malaria infection in the midgut in a rodent malaria model. The dysfunction in the salivary glands enabled the inhibition of malaria transmission to mosquito midguts. Therefore, salivary components are also important in malaria control.
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影响因子：
6.7
作者：
Ghosh, Anil K.;Devenport, Martin;Jethwaney, Deepa;Kalume, Dario E.;Pandey, Akhilesh;Anderson, Vernon E.;Sultan, Ali A.;Kumar, Nirbhay;Jacobs-Lorena, Marcelo
通讯作者：
Jacobs-Lorena, Marcelo
影响因子：
20.1
作者：
Karch J;Molkentin JD
通讯作者：
Molkentin JD
影响因子：
2.6
作者：
Mathur, G.;Sanchez-Vargas, I.;James, A. A.
通讯作者：
James, A. A.
影响因子：
2.4
作者：
Horn, C;Wimmer, EA
通讯作者：
Wimmer, EA
影响因子：
9.2
作者：
Lu, Tan;Qiu, Yu Tong;Zwiebell, Laurence J.
通讯作者：
Zwiebell, Laurence J.