Development of a Drosophila model to study vector colonization by Yersinia pestis

描述(由申请人提供)：每年，病媒传播的疾病困扰着全世界数百万人，影响到卫生保健系统和经济资源。对抗菌剂、杀虫剂和杀虫剂的抗药性是许多媒介传播疾病死灰复燃的原因之一。为了制定新的应对措施，我们必须确定扰乱这些疾病传播周期的新目标。由于缺乏可用于研究微生物-媒介相互作用的遗传工具和资源，这一努力受到了阻碍。 我们的项目旨在通过开发一种新的模式系统来克服这些障碍，在该系统中确定对鼠疫耶尔森氏菌(鼠疫病原体)与其跳蚤媒介相互作用的重要遗传因素。我们的模型系统使用果蝇--黑腹果蝇作为跳蚤的替代品。果蝇已被用作研究先天性免疫以及各种传染病的模型。我们将把苍蝇和鼠疫杆菌可用的强大基因工具与高通量技术结合起来，以确定有助于昆虫定居的途径。 这种创新的方法将在未来的工作中作为一个平台，利用整个生物体而不是模拟体外条件来研究昆虫定植的分子细节。重要的是，我们的模型系统具有高通量能力，有可能被改造成一个药物发现平台，以识别破坏鼠疫和其他疾病的微生物-媒介相互作用的化合物。

DESCRIPTION (provided by applicant): Each year vector-borne diseases afflict millions of people worldwide, impacting health care systems and economic resources. Contributing to the resurgence of many vector-borne diseases is the resistance to antimicrobials, pesticides and insecticides. In order to develop new counter-measures, we must identify new targets that disrupt the transmission cycle for these diseases. This effort is hindered by the lack of genetic tools and resources available to study the microbe-vector interactions. Our project is aimed at overcoming those obstacles by developing a new model system in which to identify genetic factors important for the interaction of Yersinia pestis (causative agent of plague) with its flea vector. Our model system employs Drosophila melanogaster, the fruit fly, as a surrogate for the flea. Drosophila has been used as a model to study innate immunity as wells as a variety of infectious diseases. We will couple the powerful genetic tools available for flies and Y. pestis with high throughput technologies to identify pathways that contribute to colonization of insects. This innovative approach will serve as a platform in future work that will investigate the molecular details of insect colonization using whole organisms, rather than simulative in vitro conditions. Importantly, our model system with its high throughput capabilities has the potential to be adapted to a drug discovery platform in order to identify compounds that disrupt the microbe-vector interaction for plague and other diseases.