Virulence mechanisms of the family pasteurellaceae

在许多动物中，扁桃体是多种细菌和病毒的重要定植部位。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，但实际上人们对这些微生物如何与扁桃体组织结合一无所知。我们的研究重点是改进猪腭扁桃体外植体模型，该模型可用于实验室研究细菌与扁桃体的相互作用。通过这些扁桃体“培养”，我们将研究猪放线杆菌和胸膜肺炎杆菌（APP）这两种密切相关的猪病原体相似的表面蛋白的作用。APP可引起非常严重的出血性肺炎；猪单胞杆菌引起一种几乎难以区分的肺炎，也可侵入血液，引起败血症、关节炎和脑膜炎等疾病。我们假设这些细菌有非常相似的表面粘附素，它们用来附着在宿主身上，但是这些蛋白质的微小差异使得这些细菌可以附着在扁桃体和其他组织的不同部位。在最近的研究中，我们发现猪单胞菌需要OmpA蛋白才能与扁桃体和脑细胞结合，但对该蛋白在APP中的作用一无所知。此外，从基因组序列信息中，我们知道猪单胞菌和APP中都存在非常相似的LamB蛋白，尽管该蛋白已被证明参与其他细菌物种的附着，但对其在放线菌物种中的作用一无所知。A. suis和APP也共享所谓的自转运蛋白，据报道，这种蛋白在其他物种中是重要的粘附蛋白。我们计划通过制造缺乏这些蛋白质的突变菌株，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，来证明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猪单胞菌和APP引起的经济上重要的疾病。

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.