Interactions between histophilus somni (haemophilus somnus) and phagocytic cells

睡眠嗜组织杆菌（睡眠嗜血杆菌）与吞噬细胞之间的相互作用

• 批准号: 3574-2008
• 负责人: Potter, Andrew
• 金额: $ 1.82万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498161
• 关键词: Interactions; between; histophilus; somni; haemophilus

Histophilus somni is a Gram negative pathogen of cattle capable of causing a variety of diseases, including infections of lung, heart, joints, brain and reproductive tract. The control of H. somni infection has been accomplished through both antibiotic treatment as well as vaccination. However, given that the prevalence of this disease syndrome has been increasing over the past decade, improved control methods are clearly needed. Central to the ability of the organism to cause disease is its capability to evade host innate immune responses, the first line of defense against bacterial pathogens. Specifically, H. somni is able to suppress the antimicrobial activities of leukocytes, including PMNs and macrophages, resulting in enhanced survival of the organism and dissemination throughout the body. It is our hypothesis that H. somni produces specific proteins capable of modifying the host innate immune response, resulting in a general suppression. In order to test this hypothesis, we will characterize new proteins produced by the bacterium while it is incubated with bovine leukocytes using both functional genomic as well as traditional protein biochemistry techniques. These proteins will be fully characterized and the genes coding for each one isolated and used to construct mutant H. somni lacking each specific gene. These will then be tested for their ability to interfere with PMN function. Finally, we will test the ability of these mutants to cause disease in a bovine infection model. Ultimately, this will lead to the development of novel targets for both vaccine and therapeutic development.

somni组织菌是牛的一种革兰氏阴性病原体，能引起多种疾病，包括肺、心脏、关节、脑和生殖道感染。通过抗生素治疗和疫苗接种，已经实现了对索姆尼嗜血杆菌感染的控制。然而，鉴于这种疾病综合征的流行在过去十年中有所增加，显然需要改进控制方法。生物体致病能力的核心是其逃避宿主先天免疫反应的能力，这是抵御细菌病原体的第一道防线。具体来说，H. somni能够抑制白细胞（包括pmn和巨噬细胞）的抗菌活性，从而提高生物体的存活率和在全身的传播。我们的假设是，H. somni产生能够改变宿主先天免疫反应的特定蛋白质，从而导致普遍抑制。为了验证这一假设，我们将使用功能基因组学和传统的蛋白质生物化学技术来表征细菌在与牛白细胞孵育时产生的新蛋白质。这些蛋白质将被完全表征，并分离出编码每个蛋白质的基因，用于构建缺乏每个特定基因的突变体。然后将测试它们干扰PMN功能的能力。最后，我们将在牛感染模型中测试这些突变体引起疾病的能力。最终，这将导致疫苗和治疗开发的新靶点的发展。