Virulence mechanisms of the family pasteurellaceae

在许多动物中，扁桃体是广泛的细菌和病毒定植的重要部位。 在大多数情况下，这些生物无害地存在。 然而，一些致病物种可以利用扁桃体进入宿主并引起疾病。 尽管有100多篇论文描述了哺乳动物扁桃体中存在的特定细菌，但实际上对这些生物体如何结合扁桃体组织一无所知。 我们的研究主要集中在改进猪腭扁桃体外植体模型，可用于在实验室中研究细菌扁桃体的相互作用。 利用这些扁桃体“培养物”，我们将研究猪的两种密切相关的病原体，猪放线杆菌和放线杆菌的相似表面蛋白的作用。胸膜肺炎（APP）。APP可引起非常严重的出血性肺炎;猪流感会引起一种几乎无法分辨的肺炎，也会侵入血液，引起败血症、关节炎和脑膜炎等病症。 我们假设这些细菌与生物体具有非常相似的表面粘附素，它们用于附着在宿主上，但这些蛋白质的微小差异使这些细菌能够结合到扁桃体和其他组织的不同部位。 在最近的研究中，我们发现OmpA蛋白是A.另外，根据基因组序列信息，我们知道非常相似的LamB蛋白存在于A. suis和APP，尽管该蛋白质已被证明参与其它细菌物种中的附着，但关于其在放线杆菌属物种中的作用尚不清楚。A.猪和APP还共享所谓的自转运蛋白，据报道，这些自转运蛋白是其他物种中重要的粘附素。 我们计划通过创造缺乏这些蛋白质的突变株，并测试它们与扁桃体外植体、肺和脑细胞培养物结合的能力，来显示这些假定的粘附素的作用。 通过了解这些细菌如何与宿主组织结合，这些研究应该有助于我们更好地了解和预防由A.猪和APP

In many animals, the tonsil is an important site of colonization for a wide range of bacteria and viruses. In most cases, these organisms persist harmlessly. Some pathogenic species, however, can use the tonsil to enter the host and cause disease. Although there are 100's of papers describing the presence particular bacteria in mammalian tonsils, virtually nothing is known about how these organisms bind tonsil tissue. Our studies are focused on refining a porcine palatine tonsil explant model that can be using to study bacterial-tonsil interactions in the laboratory. With these tonsil "cultures" we will investigate the role of similar surface proteins of two closely related pathogens of swine, Actinobacillus suis and A. pleuropneumoniae (APP). APP can cause a very severe hemorrhagic pneumonia; A. suis causes a virtually indistinguishable pneumonia and can also invade the bloodstream causing conditions such as septicemia, arthritis, and meningitis. We hypothesize that these to organisms have very similar surface adhesins that they use to attach to the host, but small differences in these proteins allow these bacteria to bind to different sites in the tonsil and other tissues. In recent studies, we showed that the OmpA protein is needed for A. suis to bind to tonsil and brain cells, but nothing is known about the role of this protein in APP. Also, from genome sequence information, we know that very similar LamB proteins are present in both A. suis and APP and although this protein has been shown to be involved in attachment in other bacterial species, nothing is known about its role in Actinobacillus species. A. suis and APP also share so-called autotransporter proteins that have been reported to be important adhesins in other species. We plan to show the roles of these putative adhesins by creating mutant strains that lack these proteins and testing their ability to bind to tonsil explants and to lung and brain cell cultures. By learning how these bacteria bind to host tissues, these studies should help us to better understand and prevent the economically important diseases caused by A. suis and APP.