19-BBSRC-NSF/BIO Bacterial and host genetic factors contributing to microbiome acquisition and homeostatis in mosquitoes

动物的肠道微生物群落对它们的健康至关重要。然而，在大多数宿主系统中，这些群落如何在肠道中聚集的潜在机制在很大程度上仍未被探索。拟议的研究建立在现有生产性合作的基础上，以扩大我们对宿主如何控制细菌在肠道的定植的知识，反过来，细菌如何适应肠道与宿主形成稳定的联系。到目前为止，共同进化几乎只在高度稳定、长期关联的细菌伙伴中进行研究，例如专性人类病原体或垂直传播的专性共生体。在这里，我们假设宿主-微生物区系的共同适应也可以发生在宿主个体生命周期的非常短的时间尺度上的重复相互作用中，并且很可能是由宿主和细菌的遗传因素介导的。我们将在埃及伊蚊上阐述我们的中心假设，这是一种令人感兴趣的昆虫，因为成年雌性可以传播寨卡病毒、登革热和其他导致人类严重疾病的虫媒病毒。蚊子是检验我们假设的理想系统，因为它们拥有简单的肠道群落，其中包含每个都可以培养和操纵的细菌分类群。也存在产生含有特定细菌群落的无菌(无微生物)和共生蚊子的方法。因为两人都是。埃及伊蚊及其相关的肠道细菌在基因上是易驯化的，拟议的研究提供了一种独特的、深入的宿主-微生物基因相互作用的机制研究，这些基因在大多数系统中很难研究。

Animals harbor gut microbial communities that are essential for their fitness. However, the mechanisms underlying how these communities assemble in the gut remain largely unexplored in most host systems. The proposed research builds on existing productive collaborations to expand our knowledge of how hosts control gut colonization by bacteria and, conversely, how bacteria adapt to the gut to form stable associations with hosts. To date, coevolution has almost exclusively been investigated in bacterial partners of highly stable, long-term associations such as obligate human pathogens or vertically transmitted obligate symbionts. Here, we hypothesize that host-microbiota coadaptation can also occur over repeated interactions spanning only very short time scales of the hosts' individual life span and islikely mediated by genetic factors of both hosts and bacteria. We will address our central hypothesis in the mosquito Aedes aegypti, an insect of interest because adult females can transmit Zika, dengue, and other arboviruses that cause severe disease in humans. Mosquitoes are an ideal system in which to test our hypothesis because they harbor simple gut communities containing bacterial taxa that can each be cultured and manipulated. Methods also exist to generate axenic (microbe-free) and gnotobiotic mosquitoes containing defined bacterial communities. Because both Ae. aegypti and its associated gut bacteria are genetically tractable, the proposed research provides a unique, in-depth mechanistic study of host-microbe gene interactions that are difficult to study in most systems.