Role of the Gut Microbiome in Mosquito Development

肠道微生物组在蚊子发育中的作用

• 批准号: 10454247
• 负责人: Michael Strand
• 金额: $ 35.5万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454247
• 关键词: Adult; Aedes; Affect; Alternative Splicing; Anopheles gambiae; Arthropod Vectors; Award; Bacteria; Bacterial Genes; Biological Assay; Biology; Blood; Cell Respiration; Communities; Complex; Consumption; Culicidae; Development; Diet; Disease; Disease Vectors; Environment; Escherichia coli; Exhibits; Fat Body; Female; Foundations; Funding; Gastrointestinal tract structure; Gene Activation; Genes; Genetic Screening; Gnotobiotic; Goals; Gram-Negative Bacteria; Growth; High-Throughput Nucleotide Sequencing; Human; Hypoxia; Individual; Intestines; Invertebrates; Laboratory culture; Larva; Length; Link; Lipids; Measures; Mediating; Metabolism; Methods; Microbe; Midgut; Molecular; Molecular Target; Molting; Nutrient; Nutritional; Organism; Outcome; Oxygen; Pathway interactions; Physiology; Population; Process; Progress Reports; Protein Isoforms; Quality Control; Regulatory Pathway; Reporting; Resources; Risk; Role; SECTM1 gene; Series; Signal Pathway; Signal Transduction; Source; Structure; Tissues; Vertebrates; Work; activating transcription factor; base; chromatin immunoprecipitation; disorder control; experimental study; fitness; gut microbes; gut microbiome; gut microbiota; human disease; improved; innovation; insight; lipid biosynthesis; member; pathogen; programs; stem cell proliferation; transcription factor; transmission process; vector; vector control; vector mosquito

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.

项目概要 蚊子被公认为是最重要的节肢动物致病媒介 病原体。这是因为大多数物种在成年雌性时必须以脊椎动物的血液为食 复制。反过来，食用多次血粉会导致病原体传播 宿主之间，而载体丰度影响传播风险。因此，接近 破坏病原体传播和/或减少媒介种群都是策略 疾病控制。蚊子的消化道中寄生着微生物，这些微生物共同形成了肠道 微生物群。本申请是一项续订请求，旨在继续我们在以下方面的重要作用： 蚊子发育中的肠道微生物群。我们目前的奖项主要针对埃及伊蚊， 它是多种人类疾病的主要媒介。我们迄今为止的研究表明微生物 诱导的肠道缺氧起到生长信号的作用，并且该信号的转导 蚊子幼虫需要缺氧诱导的转录因子（HIF）。结果进一步表明 HIF 信号激活多个在营养获取中发挥重要作用的过程， 生长和新陈代谢。该提案的总体目标是解开分子 将微生物引起的肠道缺氧和 HIF 信号与营养物质和营养物质联系起来的机制 调节生长的信号通路。拟议的研究有潜力 对了解肠道微生物群在大多数发育中的作用具有变革性影响 如果不是所有媒介蚊子种类。拟议的具体目标是： 1. 鉴定Ae中的HIF靶基因。埃及伊蚊。 2. 表征 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。 预期结果将确定扰乱蚊子发育的分子靶标 可以改善蚊子饲养以进行控制计划的因素。结果也将指导 了解饮食和肠道微生物群如何调节所有蚊子种类的生长。