按蚊是疟疾等多种疾病的传播媒介，蚊虫防治是阻断疾病传播的主要措施。由于蚊虫抗药性的产生，急需新方法防治蚊虫和阻断疟疾传播。近来研究表明，球孢白僵菌在成蚊的生物防治和阻断疟疾传播上有广阔的应用前景。肠道共生菌在按蚊免疫和病原菌感染中发挥重要的作用。我们最近发现肠道共生菌在白僵菌感染按蚊中起到促进作用，这一新现象及其相关的分子机制未见报道。本项目以肠道共生菌-按蚊-白僵菌三者互作为模型，通过16S rDNA测序和体外分离培养的方法解析白僵菌感染按蚊后肠道菌群结构的变化，揭示在白僵菌杀蚊中起关键作用的肠道菌群与作用机制；通过比较转录组分析肠道共生菌对白僵菌感染引起按蚊系统免疫和肠道免疫应答的影响和调控机制，解析白僵菌感染按蚊后免疫变化与肠道菌群失衡的内在联系和分子机制，阐明肠道共生菌加速白僵菌杀蚊的分子机理，为研发蚊虫生物防治新策略提供理论依据，为揭示病原真菌与按蚊互作的分子机理提供新的视角。

Anopheles mosquitos serve as vectors of malaria and many other human pathogens of public health importance, mosquito vector control is the key to block the disease transmission. Continuous emergence and rapid spread of insecticide-resistant mosquitoes strongly challenges the fight against mosquito-borne diseases, in particular malaria, new methods to control adult mosquito are urgently needed. Recent studies have shown that the entomopathogeni fungus Beauveria bassiana holds promise as biological insecticide to control both insecticide-susceptible and insecticide-resistant adult mosquito, and significantly reduce malaria transmission intensity. Furthermore, emerging data suggest that mosquito gut microbiota play important roles in regulation of the insect host’s immune system, and interaction with pathogens. We have recently found that the gut microbiota facilitate Beauveria bassiana to kill Anopheles mosquito. The new phenomenon and its associated molecular mechanisms have not been reported. In this study, we will plan to determine the dynamic gut microflora of the adult mosquitoes after infected by Beauveria bassiana using 16S rRNA gene based pyrosequencing and culture-dependent methods, and further identify the gut bacteria that play a key role in assisting Beauveria bassiana to kill mosquito, and elucidate the related mechanisms. Whole transcriptome sequencing (RNA-seq) analysis will be used to comprehensively analyze the changes and mechanisms of sytemic immune and gut epithelial immune response to Beauveria infection, dissect the correlation between dysbiosis of the gut microbiota and mosquito immune changes by fungal infection, and elucidate the melecular mechanisms by which gut microbiota facilitate Beauveria bassiana to kill Anopheles mosquito. This project will help deepen our understanding of the tripartite interactions between gut microbiota, mosquito and fungal pathogen, providing the foundation and new perspectives to control mosquito and prevent mosquito borne disease transmission.