Molecular Improvement of Bacterial Mosquito Larvicides

描述（由申请人提供）： 拟议的研究是开发更有效和环境安全的 用于控制人类主要蚊媒的重组细菌 疾病包括疟疾、丝虫病、登革热和病毒性脑炎。 这些细菌将比芽孢杆菌更具成本效益 苏云金杆菌subsp israelensis（Bti）和Bacillussphaericus（Bs 目前用于病媒控制项目的物种。此外，本发明还提供了一种方法， 它们将更不容易诱导蚊子产生抗药性， 发展到B。在巴西库蚊的野外种群中， 中国和印度。为了支持这些新细菌的可持续利用， 为了控制病媒，将使用新的杀虫蛋白组合 评估针对以下问题的有效性和耐药性管理策略： 控制属于最重要媒介属的蚊子种类， 即按蚊、伊蚊和库蚊。开发和使用这些新的 重组将加强研究，重点是提高我们的知识， 导致高毒性的协同作用的潜在机制， CytlA蛋白延迟、避免或克服载体中抗性的能力 其他细菌内毒素。这些目标将会实现 通过一个全面的研究计划，包括以下三个 具体目标：（1）构建基于以下的改进的细菌杀虫剂： 杀蚊内毒素的新组合;（2）靶标的测定 细菌重组体的谱和毒性;和（3）测定 CytlA协同内毒素和克服内毒素的一般机制 阻力通过这项研究开发的细菌杀虫剂应该 导致改进病媒控制和减少疾病，同时 减少使用广谱合成 化学杀虫剂此外，杀虫蛋白组合物 确定优化疗效和耐药性管理将提供模型 用于工程化细菌和藻类的田间种群以控制病媒，以及 转Bt基因作物的抗性管理项目。

DESCRIPTION (provided by the applicant): The long-term objectives of the proposed research are to develop more effective and environmentally safe recombinant bacteria for controlling the mosquito vectors of major human diseases including malaria, filariasis, dengue, and the viral encephalitides. These bacteria will be significantly more cost-effective than Bacillus thuringiensis. subsp israelensis (Bti) and Bacillussphaericus (Bs), the two species currently used in operational vector control programs. In addition, they will be much less prone to induce mosquito resistance, which has already developed to B. sphaericus in field populations of Culex mosquitoes in Brazil, China, and India. To support the sustainable use of these new bacteria in vector control programs, novel combinations of insecticidal proteins will used to be evaluate efficacy and resistance management strategies aimed at controlling mosquito species belonging to the most important vector genera, namely, Anopheles, Aedes, and Culex. The development and use of these new recombinants will be enhanced by studies focusing on improving our knowledge of mechanisms underlying the synergism responsible for the high toxicity and capacity of the CytlA protein to delay, avoid, or overcome resistance in vector populations to other bacterial endotoxins. These objectives will be achieved through a comprehensive research program consisting of the following three specific aims: (1)Construction of improved bacterial insecticides based on novel combinations of mosquitocidal endotoxins; (2) Determination of the target spectrum and toxicity of the bacterial recombinants; and (3) Determination of the general mechanism by which CytlA synergizes endotoxins and overcomes resistance. Bacterial insecticides developed through this research should result in improved vector control and disease reduction, with concomitant health benefits accruing from reductions in the use of broad-spectrum synthetic chemical insecticides. Moreover, the insecticidal protein combinations identified to optimize efficacy and resistance management will provide models for engineering field populations of bacteria and algae for vector control, and for resistance management programs for Bt transgenic crops.