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

许多传染病影响牲畜，不仅影响动物的健康和福利，而且影响我们农业的经济可持续性。在重要的动物病原体中，有一些细菌生活在宿主细胞内并完全依赖于宿主细胞。这些所谓的“专性细胞内”细菌很难处理，因此要了解如何帮助改善动物健康是非常困难的。由于这种类型的病原体必须感染宿主动物才能生存，它们通常会发展出一种机制，非常有效地进入并接管宿主细胞，并逃避宿主的防御。专性细胞内细菌中，流产衣原菌（Chlamydophila abortus）和细胞内Lawsonia胞内菌（Lawsonia胞内菌）分别在绵羊和猪中非常普遍。由于受影响的动物比例如此之高，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。虽然针对这些病原体的疫苗是可用的，但它们有缺点，所以最终，我们希望开发有效的方法来非常有效地减少这些疾病的影响。由于这些细菌很难处理，使用高科技基因组方法可以是非常经济有效的方法，可以提高对感染中重要成分的了解，并在控制疾病方面取得新进展。基因组序列提供了关于病原体的丰富信息，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——这可能与致病有关。基因组的分析是非常有用的，但是当它与对基因蛋白质产物功能的理解相结合时，它的价值是最大的。我们打算使用基于计算机的方法和实验室方法来研究这个蛋白质家族，以获得对这些V型蛋白质的理解。这些蛋白质存在于细菌表面，通常会被宿主的防御系统识别，并导致宿主激活防御系统以防止感染。改变这些蛋白质的能力可能是“伪装”病原体的一种重要方式，使它们能够逃脱宿主的防御。C. abortus和L. intraculularis都有许多这种V型蛋白的成员，因此我们认为很可能这种家族的成员存在于细菌表面会有所不同。通过了解这些蛋白质在每个物种中的存在是如何变化的，我们将能够确定对感染最重要的家族成员，从而改进对这些重要牲畜疾病的检测、治疗或预防。

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.