Molecular Improvement of Bacterial Mosquito Larvicides

简介(由申请人提供)： 拟议的研究是为了开发更有效和更环保的 控制人类主要蚊媒的重组细菌 疟疾、丝虫病、登革热和病毒性脑炎等疾病。 这些细菌将比芽孢杆菌更具成本效益 苏云金杆菌。以色列亚种(Bti)和球形芽孢杆菌(Bs) 目前在病媒生物控制方案中使用的物种。此外, 它们将不太容易引发蚊子耐药性，而蚊子耐药性已经 在巴西库蚊的野外种群中发展为球形球状芽孢杆菌， 中国和印度。支持这些新细菌的可持续使用 病媒控制计划，将使用杀虫蛋白的新组合 要评估疗效和耐药性管理策略，旨在 控制属于最重要的媒介属的蚊子物种， 即按蚊、伊蚊和库蚊。这些新技术的开发和使用 重组体将通过专注于提高我们对 导致高毒性和高毒性的协同作用的潜在机制 CytlA蛋白在载体中延迟、避免或克服抗药性的能力 种群对其他细菌内毒素的影响。这些目标将会实现 通过由以下三项组成的综合研究计划 具体目标：(1)构建新型细菌杀虫剂 灭蚊内毒素的新组合；(2)靶标的确定 细菌重组体的光谱和毒性；(3)细菌重组体的测定 CytlA协同内毒素和克服内毒素的一般机制 抵抗。通过这项研究开发的细菌杀虫剂应该 结果改善了媒介控制和减少了疾病，并伴随而来 减少使用广谱合成药物对健康的好处 化学杀虫剂。此外，杀虫蛋白组合 确定以优化疗效和耐药性管理将提供模式 用于工程现场的细菌和藻类种群以控制病媒，以及 用于Bt转基因作物的抗性管理计划。

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.