Role of the Gut Microbiome in Mosquito Development

项目摘要 蚊子是最重要的节肢动物媒介 病原体这是因为大多数物种必须以成年雌性脊椎动物的血液为食， 繁殖。反过来，多次进食血液会使病原体传播 而病媒丰度影响传播风险。因此， 破坏病原体传播和/或减少病媒种群都是 疾病控制。蚊子的消化道中有微生物，这些微生物共同组成了肠道 微生物群本申请是一个更新的请求，以继续我们的工作的重要作用， 肠道微生物群在蚊子发育中的作用我们目前的奖项重点是埃及伊蚊， 它是几种人类疾病的主要传播媒介。我们的研究表明微生物- 诱导的肠道缺氧作为生长信号起作用，并且该信号在细胞中的转导， 蚊子幼虫需要低氧诱导的转录因子（HIF）。结果进一步表明 HIF信号激活了几个在营养获取中起重要作用的过程， 生长和新陈代谢。这项提案的总体目标是解开分子 将微生物诱导的肠道缺氧和HIF信号传导与营养物质联系起来的机制， 调节生长的信号通路。拟议的研究有可能 对理解肠道微生物群在大多数疾病发展中的作用产生了变革性影响。 如果不是所有病媒蚊子物种。拟议的具体目标是： 1.鉴定Ae.埃及人。 2.描述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.评估肠道微生物群作为蚊子发育营养源的作用。 预期成果将确定干扰蚊子发育的分子靶点， 这些因素可以改善蚊子饲养的控制计划。结果还将指导 了解饮食和肠道微生物群如何调节所有蚊子物种的生长。

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.