Evaluation of a novel mosquito repellent isolated from bacteria

从细菌中分离出的新型驱蚊剂的评价

• 批准号: 9091861
• 负责人: HEIDI GOODRICH-BLAIR
• 金额: $ 18.07万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091861
• 关键词: Adoption; Adult; Aedes; Amino Acid Sequence; Antibiotics; Bacteria; Biological Assay; Brazil; Candidate Disease Gene; Categories; Cell Line; Cell Survival; Cells; Chemical Structure; Chemicals; Culicidae; Data; Dengue; Desiccation; Disease; Disease Outbreaks; Disease Vectors; Enzymes; Evaluation; Female; Fever; Future; Gene Cluster; Genes; Genome; Goals; Health system; Human; Individual; Infection; Insect Repellents; Longevity; Malaria; Mammalian Cell; Marketing; Methods; Microbe; Mosquito-borne infectious disease; NMR Spectroscopy; North America; Nuclear; Nuclear Magnetic Resonance; Peptides; Pesticides; Pharmaceutical Preparations; Plants; Production; Public Health; Reporting; Research; Resistance; Site-Directed Mutagenesis; Source; Spectrum Analysis; Structure; Toxic effect; United States; Vaccines; Water; West Nile Fever; Xenorhabdus; Yellow Fever; Zika Virus; base; chemical synthesis; chikungunya; disorder prevention; feeding; microbial; novel; peptide synthase; prevent; public health relevance; sugar; vector mosquito

 DESCRIPTION (provided by applicant): The recent outbreaks of West Nile fever and Chikungunya fever in North America created a new challenge for the public health system in the United States. The lack of vaccines and treatment options for these diseases raises the importance of personal protection against the mosquito vectors. N,N-diethyl-meta-toluamide (DEET) is the most effective mosquito repellent currently on the market. However, decreasing consumer acceptance of DEET has led to a search for new types of repellents. Serendipitously, we screened several isolates of entomopathogenic bacteria for adulticidal activity and found potent mosquito repellent activity in an extract from Xenorhabdus innexi. Female Aedes aegypti died of desiccation rather than accept sugar water mixed with the bacterial extract. Preliminary data indicate that the active compound is a small peptide and the purified peptide is water soluble and retains repellent activity for at least several weeks. Three specific aims are proposed to further our understanding of the molecule. Aim 1 will use nuclear magnetic resonance (NMR) spectroscopy methods to resolve the structure of the purified repellent peptide. Aim 2 will identify the biosynthetic gene cluster involved in the repellent peptide production in X. innexi, which will enable searches for similar gene clusters in other bacterial species as well as mutagenic approaches for structure/function analyses. Aim 3 will further characterize the novel repellent compound. Here, the efficacy and longevity of the repellent activity will be quantified against several key vector mosquito species. In addition, cell viabilit assays will be performed against several mammalian cell lines to examine the toxicity profile of the repellent peptide. The information generated in this study will contribute to our understanding of a new category of mosquito repellents and may ultimately result in new products for protection against mosquito vectors.