BIOLOGY OF TREMATODE-SNAIL ASSOCIATIONS

摘要：该项目的长期目标是更好地了解蜗牛传播的蠕虫的生物学。 继续造成重大负担的寄生虫，如曼氏血吸虫。‘中国的人类健康 发展中国家的大部分地区。我们打算了解淡水蜗牛BiomphalariJrfj/Labrata是如何防御的 免受曼氏吸虫和相关吸虫--帕氏棘口吸虫的感染。通过理解 宿主防御和寄生虫传染性的潜在机制，我们将增加实现 有效的新的控制措施。另一个重要目标是发展和保持在以下领域的专门知识 蜗牛传播的病原体。在这项经过广泛修订的提案中，使用我们开发的新方法，以及 利用qPCR、微阵列和蛋白质组学等强大的工具，我们解决了以下三个具体目标 直接与这个研究项目的基础有关，蜗牛防御 吸虫感染，以及吸虫如何克服或改变这些。对于大部分概述 研究中，我们强调对某一品系的钉螺感染前后进行比较，从而避免 与品系间比较相关的外部变量。对于第一个目标，我们假设之前 暴露于吸虫幼虫可引起光滑拟青虫的获得性抗性状态。这提供了一种 从独特的角度了解耐药性，我们建议将 对幼年钉螺具有获得性抵抗力的钉螺对吸虫攻击的反应 达到了高度抵抗的状态。我们的第二个目标是致力于揭示 破坏蜗牛防御的幼虫吸虫。我们建议检验我们早先的假设，即曼氏葡萄球菌是一种 “隐形”寄生虫在很大程度上避免了在蜗牛宿主中被发现，而帕伦索埃希氏菌则引发了戏剧性的 反应，但随后依靠免疫抑制策略生存。我们还将研究帕伦索肠杆菌是如何 干扰光滑假单胞菌萨尔瓦多株对曼氏假单胞菌的先天抗性。第一部分 我们的第三个目标是开发分子技术来更准确地监测曼氏葡萄球菌的命运。 蜗牛体内的孢子囊。这项工作是这一目标的第二部分的必要前奏，也就是理解 一种被低估但却很重要的现象，可能会限制感染血吸虫的蜗牛的数量 在自然界中，即相当大比例的血吸虫感染在个体中不可避免地失败 来自其他被认为是易受影响的种群的蜗牛。通过使用吸虫-蜗牛的新方法 随着研究的深入，我们将对这些宿主-寄生虫的相互作用获得广泛和包容的新概述。还有，这些工具 这一结果将为今后研究血吸虫与蜗牛的相互作用奠定基础。我们的研究也将 为即将到来的光滑假单胞菌基因组测序项目提供了有价值的补充。

ABSTRACT: The long-term goal of this project is to better understand the biology of snail-borne helminth parasites such as Schistosoma mansoni that continue to impose a significant burden or. 'human health in much of the developing world. We intend to learn how the freshwater snail BiomphalariJrfj/labrata defends itself from infection by S. mansoni and the related trematode, Echinostoma paraensei. By understanding the underlying mechanisms of host defense and parasite infectivity, we will increase the chances of achieving effective new control measures. Another important goal is to develop and maintain expertise in the area of snail-borne pathogens. In this extensively revised proposal, using new methods we have developed, and exploiting powerful tools such as qPCR, microarrays and proteomics, we address three specific aims that relate directly to what have always been the foundation of this research program, snail defenses against trematode infection, and how these are overcome or modified by trematodes. For most of the outlined studies, we emphasize before and after infection comparisons of snails of a particular strain, thus avoiding extraneous variables associated with inter-strain comparisons. For the first aim,we hypothesize that prior exposure to trematode larvae can provoke a state of acquired resistance in B. glabrata. This provides a unique vantage point from which to understand resistance in general, and we propose to compare the responses to trematode challenge of snails with acquired resistance to those of naive snails, to learn how a state of heightened resistance is achieved. Our second aim is devoted to revealing the mechanisms used by larval trematodes in subverting snail defenses. We propose to test our earlier hypothesis that S. mansoni is a "stealth" parasite that largely avoids detection in the snail host whereas E. paraensei provokes a dramatic response but then relies on immunosuppressive tactics for survival. We will also examine how E. paraensei interferes with the innate resistance shown by the Salvador strain of B. glabrata to S. mansoni. The first part of our third aim is to develop molecular techniques to more precisely monitor the fate of S. mansoni sporocysts in snails. This work is a necessary prelude to the second part of this aim which is to understand an underappreciated yet important phenomenon that likely limits the number of schistosome-infected snails in nature, namely the inevitable failure of a significant percentage of schistosome infections in individual snails from populations otherwise considered to be susceptible. By using methods new to trematode-snail studies, we will gain broad and inclusive new overviews of these host-parasite interactions. Also, the tools generated will be useful for future studies of schistosome-snail interactions in the field. Our studies will also provide a valuable complement to the upcoming genome sequencing project for B. glabrata.