Integrated genomic and proteomic characterisation of autotransporter proteins of obligate intracellular bacteria C. abortus and L. intracellularis

专性胞内细菌 C. abortus 和 L. intracellularis 的自转运蛋白的综合基因组和蛋白质组学特征

• 批准号: BB/E018939/1
• 负责人: David Longbottom
• 金额: $ 181.81万
• 依托单位: Moredun Research Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE018939%2F1
• 关键词: Integrated; genomic; proteomic; characterisation; autotransporter; Integrated; genomic; proteomic; characterisation; autotransporter

Many infectious diseases affect livestock and impact not only on the health and welfare of animals but also on the economic sustainability of our agriculture industry. Among important animal pathogens are some bacteria that live within and are entirely dependent upon host cells. These so-called 'obligate intracellular' bacteria are very difficult to work with hence gaining understanding to aid in improving animal health is very problematic. Since this type of pathogen must infect a host animal to survive they typically develop mechanisms to very efficiently enter and take over host cells and evade the host's defences. Among the obligate intracellular bacteria, Chlamydophila abortus and Lawsonia intracellularis are very highly prevalent in sheep and pigs, respectively. Since such a high proportion of animals are affected, these infections have a considerable effect on animal health, quality of life and productivity. Although vaccines to these pathogens are available these have shortcomings so ultimately, we would like to develop efficient methods to very effectively reduce the effects of these diseases. Since these bacteria are difficult to work with, use of high-technology genomic methods can be very cost-effective and productive ways to improve the understanding of components with important roles in infection and make new developments in controlling disease. Genome sequences provide a wealth of information about pathogens and from this information we have identified a family of components - so-called Type V secretion proteins - which are likely to be involved in causing disease. Analysis of genomes is very informative however this is of greatest value when combined with an understanding of the function of the protein products of genes. We intend to study this family of proteins using computer-based approaches and laboratory methodologies to gain comprehension of these Type V proteins. These proteins are present on the surface of bacteria and, typically, are recognised by host defences and can result in the host activating defences that protect against infection. The ability to vary these proteins can be an important way to 'camouflage' pathogens allowing them to escape from host defences. Both C. abortus and L. intracellularis have many members of these Type V proteins thus we consider it is very likely that the members of this family present on the bacteria surface will vary. By gaining an understanding of how the presence of these proteins varies in each of these species we will be in a position to define the family members that are most important to infection and therefore lead to improved detection, treatment or prevention of these important livestock diseases.

许多传染病不仅会影响牲畜和影响动物的健康和福利，还影响我们的农业行业的经济可持续性。重要的动物病原体中有一些生活在内部并完全取决于宿主细胞的细菌。这些所谓的“细胞内”细菌很难与获得理解以帮助改善动物健康的理解非常有问题。由于这种类型的病原体必须感染宿主动物以生存，因此通常会开发机制，以非常有效地进入和接管宿主细胞并逃避宿主的防御能力。在强制性细胞内细菌中，毛细血管菌和劳森氏菌分别在绵羊和猪中非常普遍。由于影响很高的动物受到影响，因此这些感染对动物健康，生活质量和生产力产生了相当大的影响。尽管可以使用这些病原体的疫苗，但最终存在这些缺点，我们希望开发有效的方法以非常有效地减少这些疾病的影响。由于这些细菌很难与之作用，因此使用高科技基因组方法可能是非常成本效益且有效的方法，可以提高对感染中重要作用的成分的理解，并在控制疾病中发展新的发展。基因组序列提供了有关病原体的大量信息，从这些信息中，我们已经确定了一个成分家族 - 所谓的V型分泌蛋白 - 可能与引起疾病有关。基因组的分析非常有用，但是当了解基因蛋白质产物的功能时，这是最大的值。我们打算使用基于计算机的方法和实验室方法来研究这种蛋白质家族，以了解V型蛋白质。这些蛋白质存在于细菌的表面上，通常是通过宿主防御识别的，可以导致宿主激活防御剂，以防止感染。改变这些蛋白质的能力可能是“伪装”病原体的重要方法，使其可以摆脱宿主防御能力。 abortus c. c. c.c。ellicellularis都有许多V型蛋白质中的许多成员，因此我们认为，存在于细菌表面上的该家族的成员很可能会有所不同。通过了解这些蛋白质的存在如何在这些物种中有何不同，我们将有能力定义对感染最重要的家庭成员，从而改善了检测，治疗或预防这些重要的牲畜疾病。