Vector Population Modification Using Wolbachia Symbionts

描述（由申请方提供）：细胞内沃尔巴克氏体细菌感染各种无脊椎动物宿主，包括医学上重要的疾病载体。许多沃尔巴克氏体感染引起细胞质不相容性，这有效地使携带不同感染类型的宿主个体之间的交配不育。我们最近开发了一个模型，定义了沃尔巴克氏体感染频率和宿主种群大小之间的关系。模型模拟预测了一种抑制昆虫种群的新策略。这种策略是基于人工延长当两种或更多种不相容的沃尔巴克氏体感染宿主种群时发生的不稳定共存，导致宿主种群抑制。由于沃尔巴克氏体自然发生在广泛的无脊椎动物中，这种策略可能适用于各种医学和经济上重要的系统。除了种群抑制策略之外，种群替代策略还提出采用沃尔巴克氏体作为传播所需基因型的载体（例如，对疾病传播的抵抗力）进入病媒种群。在概述的研究中，我们将开发，测试和评估种群抑制和替代策略预测的模型模拟的媒介蚊子库蚊尖音。库蚊由于其作为疾病媒介的重要性以及在天然存在的库蚊种群中存在多种不相容的沃尔巴克氏体感染，因此选择尖音库蚊作为初始靶标。其他实验将研究延缓、阻止或逆转基于沃尔巴克氏体的人口更替的策略。后一种战略是一种适当的保障措施，如果人口更替带来意外的负面后果，则可能证明是必要的。为了改进战略设计、实施和评估，目标将包括更好地确定库蚊/沃尔巴克氏体共生的感染动态（例如，母亲传播率和沃尔巴克氏体对宿主适应性的影响），简化库蚊感染类型之间的区分，并改进沃尔巴克氏体控制策略的田间笼评估方法。

DESCRIPTION (provided by the applicant): Intracellular Wolbachia bacteria infect a diverse range of invertebrate hosts, including medically important disease vectors. Many Wolbachia infections cause cytoplasmic incompatibility, which effectively sterilizes mating between host individuals that harbor differing infection types. We have recently developed a model that defines the relationship between the Wolbachia infection frequency and host population size. Model simulations predict a novel strategy for suppressing insect populations. This strategy is based upon artificially prolonging an unstable coexistence that occurs when two or more incompatible Wolbachia types infect a host population, resulting in host population suppression. As Wolbachia occurs naturally within a broad range of invertebrates, this strategy is potentially applicable to a variety of medically and economically important systems. In addition to population suppression strategies, population replacement strategies propose to employ Wolbachia as a vehicle for spreading desired genotypes (e.g., refractoriness to disease transmission) into vector populations. In the outlined research, we will develop, test and evaluate population suppression and replacement strategies predicted by model simulations in populations of the vector mosquito Culex pipiens. Cx. pipiens has been selected as the initial target due to its importance as a disease vector and the availability of multiple, incompatible Wolbachia infections in naturally occurring Culex populations. Additional experiments will examine strategies for retarding, arresting or reversing Wolbachia-based population replacement. The latter strategies represent an appropriate safeguard that may prove necessary if unexpected, negative consequences become associated with population replacement. To improve strategy design, implementation, and evaluation, aims will include better defining the infection dynamics of the Culex/Wolbachia symbiosis (e.g., maternal transmission rates and Wolbachia effects on host fitness), simplifying discrimination between Culex infection types, and improving methods for field cage evaluation of Wolbachia control strategies.