Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17504-9. doi: 10.1073/pnas.1316709110. Epub 2013 Oct 7.
Anopheles gambiae is a major vector mosquito for Plasmodium falciparum, the deadly pathogen causing most human malaria in sub-Saharan Africa. Synthesized in the fat body, trehalose is the predominant sugar in mosquito hemolymph. It not only provides energy but also protects the mosquito against desiccation and heat stresses. Trehalose enters the mosquito hemolymph by the trehalose transporter AgTreT1. In adult female A. gambiae, AgTreT1 is predominantly expressed in the fat body. We found that AgTreT1 expression is induced by environmental stresses such as low humidity or elevated temperature. AgTreT1 RNA silencing reduces the hemolymph trehalose concentration by 40%, and the mosquitoes succumb sooner after exposure to desiccation or heat. After an infectious blood meal, AgTreT1 RNA silencing reduces the number of P. falciparum oocysts in the mosquito midgut by over 70% compared with mock-injected mosquitoes. These data reveal important roles for AgTreT1 in stress adaptation and malaria pathogen development in a major vector mosquito. Thus, AgTreT1 may be a potential target for malaria vector control.
冈比亚按蚊是恶性疟原虫(导致撒哈拉以南非洲大部分人类疟疾的病原体)的主要传播媒介蚊子。三塘是脂肪体中合成的主要糖,是蚊子血淋巴中的主要糖分。它不仅提供能量,还保护蚊子免受干燥和热应激的影响。三塘通过三塘转运蛋白 AgTreT1 进入蚊子血淋巴。在成年雌性冈比亚按蚊中,AgTreT1 主要在脂肪体中表达。我们发现,AgTreT1 的表达受环境压力的诱导,如低湿度或高温。AgTreT1 RNA 沉默使血淋巴中的三塘浓度降低 40%,并且在暴露于干燥或热应激后,蚊子更快死亡。在感染性血液餐之后,与模拟注射的蚊子相比,AgTreT1 RNA 沉默使蚊子中肠中的疟原虫卵囊数量减少了 70%以上。这些数据表明,AgTreT1 在主要传播媒介蚊子的应激适应和疟疾病原体发育中起着重要作用。因此,AgTreT1 可能是疟疾媒介控制的一个潜在目标。