Role of the Gut Microbiome in Mosquito Development

项目摘要 蚊子被公认为是最重要的致病节肢动物媒介 病原体。这是因为大多数物种作为成年雌性动物必须以脊椎动物的血液为食 繁殖。反过来，食用多份血粉会导致病原体传播。 在宿主之间传播，而媒介丰富度影响传播风险。因此，方法是 阻断病原体传播和/或减少媒介种群都是 疾病控制。蚊子在它们的消化道中寄生微生物，这些微生物共同形成肠道 微生物区系。这份申请是一份续订申请，以继续我们关于 蚊子发育过程中的肠道微生物群。我们目前的奖项主要是埃及伊蚊， 它是几种人类疾病的主要传播媒介。我们到目前为止的研究表明微生物- 诱导肠道缺氧作为生长信号发挥作用，该信号在体内的转导 蚊子幼虫需要低氧诱导转录因子(HIF)。结果进一步表明 HIF信号激活了几个在营养获取中起关键作用的过程， 生长和新陈代谢。这项提议的总体目标是解开分子 微生物诱导的肠道缺氧和HIF信号与营养物质和 调节生长的信号通路。拟议中的研究有可能 对理解肠道微生物区系在MOST发育中的作用的变革性影响 如果不是所有媒介蚊子物种。拟议的具体目标是： 1.鉴定Ae中HIF靶基因。埃及伊蚊。 2.刻画了Ae.埃及伊蚊HIF-α亚型。 3.分析HIF信号在脂肪生成和中肠生长中的作用。 4.评估肠道微生物区系作为蚊子发育的营养来源的作用。 预期结果将确定干扰蚊子发育的分子靶点和 可以改善蚊子饲养的因素，以控制计划。结果也将指导 了解饮食和肠道微生物区系如何调节所有蚊子种类的生长。

Project Summary Mosquitoes are well recognized as the most important arthropod vectors of disease-causing pathogens. This is because most species must feed on vertebrate blood as adult females to reproduce. In turn, consumption of multiple blood meals enables pathogen transmission between hosts while vector abundance influences transmission risks. Thus, approaches that disrupt pathogen transmission and/or reduce vector populations are both strategies for disease control. Mosquitoes host microbes in their digestive tract that collectively form a gut microbiota. This application is a renewal request to continue our work on the essential role of the gut microbiota in mosquito development. Our current award focuses on Aedes aegypti, which is a major vector of several human diseases. Our studies to date indicate that microbe- induced gut hypoxia functions as a growth signal, and that transduction of this signal in mosquito larvae requires hypoxia-induced transcription factors (HIFs). Results further indicate that HIF signaling activates several processes with essential roles in nutrient acquisition, growth and metabolism. The overall goal of this proposal is to unravel the molecular mechanisms that connect microbe-induced gut hypoxia and HIF signaling to the nutrients and signaling pathways that regulate growth. Proposed studies have the potential for transformative impacts on understanding the role of the gut microbiota in development of most if not all vector mosquito species. Proposed Specific Aims are to: 1. Identify HIF target genes in Ae. aegypti. 2. Characterize Ae. aegypti HIF-α isoforms. 3. Analyze the role of HIF signaling in lipogenesis and midgut growth. 4. Assess the role of the gut microbiota as nutrient source for mosquito development. Expected outcomes will identify molecular targets for disrupting mosquito development and factors that could improve mosquito rearing for control programs. Results will also guide understanding of how diet and the gut microbiota regulate growth of all mosquito species.