A semi field trial test on efficacy of transgenic antimalarial biocontrol fungi

转基因抗疟生防真菌功效的半田试验

• 批准号: 8561604
• 负责人: RAYMOND J ST LEGER
• 金额: $ 37.81万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-16 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8561604
• 关键词: Address; Adult; Africa; Anopheles gambiae; Antibodies; Antimalarials; Ants; Area; Arthropods; Beds; Biocontrols; Biology; Bite; Blood; Breeding; Burkina Faso; Chemicals; Climate; Clinical; Collaborations; Contracts; Culicidae; Data; Dengue; Developing Countries; Disease; Dose; Drug resistance; Endemic Diseases; Engineering; Environment; Environmental Risk Factor; Epidemiology; Exposure to; Filariasis; Funding; Future; Genetic Engineering; Genetically Modified Organisms; Goals; Grant; Habitats; Housing; Hybrids; Infection; Insecta; Insecticide Resistance; Insecticides; Laboratories; Malaria; Marshal; Microbe; Molecular Biology; Mosquito Control; Mosquito-borne infectious disease; Organism; Outcome; Parasites; Performance; Persons; Phase; Plant Sources; Plasmodium falciparum; Plastics; Policies; Policy Maker; Population; Prevalence; Probability; Process; Proteins; Recombinants; Reproduction spores; Research; Research Design; Resistance; Resources; Scientist; Simulate; Site; Sporozoites; System; Testing; Time; Toxin; Transgenes; Transgenic Organisms; Viral Encephalitis; Virulence; Work; Yellow Fever; density; design; disorder control; experience; field study; fighting; fungus; human disease; improved; innovation; killings; mathematical model; mortality; pathogen; programs; public health relevance; pyrethroid; research facility; skills; sugar; tool; transmission process; vector; weapons

DESCRIPTION (provided by applicant): Around 46% of the Worlds population lives in areas where mosquito-borne diseases including malaria, filariasis, viral encephalitides, dengue and yellow fever are endemic. It was recently established that the insect pathogenic fungus Metarhizium has the potential to control adult mosquitoes in an urban setting, but would work much better if its potency is increased. Using the resources of a two year R21 grant we compared mortality and malaria sporozoite prevalence in mosquitoes infected with transgenic Metarhizium strains expressing different combinations of insecticidal and anti-plasmodial proteins. Using Metarhizium to deliver arthropod toxins reduced the time it took to kill and produced a 150-fold reduction in effective spore doses. We hypothesize that under field conditions this will greatly increase the % of mosquitoes picking up a lethal infection and the effective persistence of the biopesticide. In this application, we propose a close collaboration with mosquito control expert Abdoulaye Diabates and his colleagues at Center Muraz that will enable us to evaluate the potential of transgenic Metarhizium in an area of Burkina Faso with very high densities of the malaria vector Anopheles gambiae (up to 200 bites/person/night) and Plasmodium falciparum sporozoite rates around 3%. Worldwide, GMO (genetically manipulated organisms) projects go through a review process that includes semi-field studies in a contained near-natural environment as a prerequisite for an open field release. A permit has been obtained from the Burkina Faso Ministry of Scientific Research and Innovation to build and use a malaria sphere that will consist of experimental huts (mimicking traditional housing), sugar sources (plants) for adults and created breeding sites (plastic containers), enclosed in a greenhouse frame with walls of mosquito netting to allow exposure to ambient climate conditions and simulate a natural mosquito habitat. To establish the potential value of modified fungi we will use the sphere to assess the efficacy, survivability, and environmental risk posed by pathogens engineered to express arthropod toxins in comparison with a strain with wild type virulence to insects but expressing ant-malarial proteins that reduce the parasite burden in mosquitoes by 98%. Our data will support predictive mathematical modeling of possible trials and hence provide a rational for designing future trials. These studies will 1) develop tools and test genetically engineered fungi that have the potential to greatly reduce malaria prevalence; 2) generate evidence to inform policy and attract donor funding for an open field release which will test epidemiological and clinical impact, and 3) enable scientists from a developing country to become directly involved in evaluating the potential use and application of transgenic microbes for future disease control.

描述（由申请人提供）：世界上大约 46% 的人口生活在疟疾、丝虫病、病毒性脑炎、登革热和黄热病等蚊媒疾病流行的地区。最近发现，昆虫病原真菌绿僵菌有潜力控制城市环境中的成蚊，但如果其效力增强，效果会更好。利用两年 R21 拨款的资源，我们比较了感染表达不同杀虫和抗疟原虫蛋白组合的转基因绿僵菌菌株的蚊子的死亡率和疟疾子孢子流行率。使用绿僵菌释放节肢动物毒素可缩短杀死节肢动物所需的时间，并使有效孢子剂量减少 150 倍。我们假设，在野外条件下，这将大大增加蚊子感染致命感染的百分比以及生物农药的有效持久性。在此应用中，我们建议与蚊虫控制专家 Abdoulaye Diabates 及其 Muraz 中心的同事密切合作，这将使我们能够评估转基因绿僵菌在布基纳法索疟疾媒介冈比亚按蚊密度非常高的地区的潜力（高达到 200 次/人/晚），恶性疟原虫子孢子率约为 3%。在世界范围内，转基因生物（基因操纵生物）项目都要经过审查过程，其中包括在封闭的近自然环境中进行半现场研究，作为开放现场释放的先决条件。已获得布基纳法索科学研究和创新部的许可，可以建造和使用疟疾领域，该领域将包括实验小屋（模仿传统住房）、成人糖源（植物）和创建的繁殖场所（塑料容器），封闭在带有蚊帐墙壁的温室框架中，以暴露于周围气候条件并模拟自然蚊子栖息地。为了确定改良真菌的潜在价值，我们将使用该球体来评估经工程改造表达节肢动物毒素的病原体所带来的功效、生存能力和环境风险，与对昆虫具有野生型毒力但表达抗疟疾蛋白的菌株进行比较，该菌株可减少蚊子体内的寄生虫负担减少 98%。我们的数据将支持可能的试验的预测数学模型，从而为设计未来的试验提供合理性。这些研究将1）开发工具并测试有可能大大降低疟疾流行率的基因工程真菌； 2) 生成证据来为政策提供信息并吸引捐助者资助进行公开现场发布，以测试流行病学和临床影响，以及 3) 使发展中国家的科学家能够直接参与评估转基因微生物在未来疾病中的潜在用途和应用控制。