Analysis of molecular factors influencing variability of mosquito gut microbiota

影响蚊子肠道菌群变异的分子因素分析

• 批准号: 8984824
• 负责人: Sarah M Short
• 金额: $ 5.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984824
• 关键词: Aedes; Affect; Area; Bacteria; Blood; Candidate Disease Gene; Centers for Disease Control and Prevention (U.S.); Central America; Cessation of life; Collection; Competence; Culicidae; Data; Dengue; Dengue Infection; Development; Disease; Environmental Risk Factor; Gene Chips; Gene Expression; Gene Expression Microarray Analysis; Gene Expression Profile; Genes; Genetic; Goals; Human; Immune; Immunity; Individual; Infection; Infection prevention; Knowledge; Laboratories; Locales; Malaria; Methodology; Methods; Microarray Analysis; Microbe; Midgut; Molecular; Molecular Analysis; Mosquito-borne infectious disease; North America; Physiological; Plasmodium; Population; Predisposition; Production; Public Health; Puerto Rico; RNA Interference; Reactive Oxygen Species; Research; Research Personnel; Role; Shapes; Signal Transduction; Southeastern Asia; Testing; Time; TimeLine; Vector-transmitted infectious disease; Work; base; disease transmission; disorder control; feeding; genome-wide; gut microbiota; human disease; improved; innovation; insight; interest; knock-down; meetings; microbial; microbiota; novel; pathogen; prevent; public health relevance; research study; transmission process; vector; whole genome

 DESCRIPTION (provided by applicant): Human diseases vectored by mosquitoes are a significant public health concern, and novel and innovative methods to prevent the spread of vector borne diseases are in high demand. Because these pathogens must infect a mosquito in order to be transmitted to humans, it is possible to interrupt the transmission cycle by preventing infections in mosquitoes. Recent research has demonstrated that the microbes in the mosquito gut can influence the infectivity of pathogens causing diseases such as malaria and dengue. Moreover, certain species of bacteria have been shown to have direct anti-pathogen activity on these and other vector borne diseases. Previous work has revealed that the mosquito gut microbiota can be highly variable. The present proposal aims to determine key genetic factors and predict mechanisms that underlie variability in the size and composition of the gut microbiota of Aedes aegypti mosquitoes. This will be accomplished by comparing the gene expression patterns across strains of Aedes that vary in gut microbiota size and composition. Genes of interest will be identified in an unbiased fashion, through the use of whole-genome gene expression microarray analysis, and confirmed for their role in shaping the gut microbiota using gene-specific gene expression studies and RNAi knockdown functional analyses. Candidate genes will also be tested for their implications in influencing the gut microbiota in fied mosquitoes collected in dengue endemic areas of Puerto Rico. This work will provide important insight into the molecular factors and mechanisms that shape the mosquito gut microbiota and contribute to its variability, which has been shown to influence vector competence. This information will advance our knowledge of mosquito gut immunity and will have important implications for the development of novel disease control strategies based on manipulation of the mosquito gut microbiota.

 描述（由适用提供）：蚊子培养的人类疾病是一个重大的公共卫生问题，并且可以预防媒介传播疾病传播的新颖和创新方法需求量很高。因为这些病原体必须感染蚊子才能传播给人类，所以可以通过防止 蚊子感染。最近的研究表明，蚊子中的微生物会影响导致疟疾和登革热等疾病的病原体感染。此外，某些细菌已被证明对这些媒介疾病具有直接的抗病原活性。先前的工作表明，蚊子肠道微生物群可能是高度可变的。本提案旨在确定关键的遗传因素和预测机制，这些机制是埃及埃及蚊子肠道微生物群体大小和组成的差异的基础。这将通过比较在肠道菌群大小和组成方面的埃德斯菌株之间的基因表达模式来实现。通过使用全基因组基因表达微阵列分析，将以公正的方式鉴定感兴趣的基因，并使用基因特异性基因表达研究和RNAi敲低功能分析确认其在构造肠道微生物群中的作用。还将测试候选基因在波多黎各登革热流行地区收集的蚊子中影响肠道菌群的意义。这项工作将为塑造蚊子肠道菌群的分子因素和机制提供重要的见解，并有助于其变异性，这已被证明会影响矢量能力。这些信息将提高我们对蚊子肠道免疫学的了解，并将基于对蚊子肠道巨biot的操纵的新型疾病控制策略的发展具有重要意义。