Role of the Gut Microbiome in Mosquito Development

肠道微生物组在蚊子发育中的作用

基本信息

批准号：
9804977
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
项目类别：
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/9804977
关键词：
Adult Aedes Affect Alternative Splicing Anopheles gambiae Arthropod Vectors Award Bacteria Bacterial Genes Biological Assay Biology Blood Cell Proliferation 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 Stem cells Structure Tissues Vertebrates Work activating transcription factor base chromatin immunoprecipitation disorder control experimental study feeding fitness gut microbes gut microbiome gut microbiota human disease improved innovation insight lipid biosynthesis member pathogen programs transcription factor transmission process vector vector control vector mosquito

项目摘要

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。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。破坏病原体传播和/或减少媒介种群都是策略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。该申请是一项更新请求，旨在继续我们研究微生物群的重要作用。我们目前的奖项主要针对埃及伊蚊，迄今为止，我们的研究表明微生物是多种人类疾病的主要媒介。肠道诱导的缺氧起到生长信号的作用，并且该信号的转导结果进一步表明，蚊子幼虫需要缺氧诱导的转录因子（HIF）。 HIF 信号激活多个在营养获取中发挥重要作用的过程，该提案的总体目标是阐明分子的生长和代谢。将微生物引起的肠道缺氧和 HIF 信号与营养素和营养物质联系起来的机制拟议的研究具有调节生长的信号通路的潜力。对理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，建议的具体目标是： 1. 鉴定埃及伊蚊中的 HIF 靶基因。 2. 表征埃及伊蚊 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的因素，以用于控制计划。了解饮食和肠道微生物群如何调节所有蚊子种类的生长。