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

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”细菌非常难以使用，因此获得帮助改善动物健康的理解是非常有问题的。由于这种类型的病原体必须感染宿主动物才能生存，因此它们通常会发展出非常有效地进入和接管宿主细胞并逃避宿主防御的机制。在专性细胞内细菌中，流产嗜衣原体和胞内劳森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、生活质量和生产力有相当大的影响。尽管针对这些病原体的疫苗是可用的，但这些疫苗有缺点，因此最终，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具有成本效益和生产力的方法，以提高对感染中重要作用的成分的理解，并在控制疾病方面取得新的进展。基因组序列提供了大量关于病原体的信息，从这些信息中，我们已经确定了一个家族的成分-所谓的V型分泌蛋白-这可能涉及引起疾病。基因组的分析是非常有用的，但这是最大的价值时，与基因的蛋白质产物的功能的理解相结合。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家族，以了解这些V型蛋白。这些蛋白质存在于细菌表面，通常被宿主防御系统识别，并可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”病原体的重要方式，使它们能够逃脱宿主的防御。两个C. abortus和L.胞内菌具有这些V型蛋白的许多成员，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变化。通过了解这些蛋白质在每个物种中的存在如何变化，我们将能够确定对感染最重要的家族成员，从而改善这些重要牲畜疾病的检测，治疗或预防。

项目成果

Therapeutics and Control of Sheep and Goat Diseases, An Issue of Veterinary Clinics: Food Animal Practice

绵羊和山羊疾病的治疗和控制，兽医诊所的一个问题：食用动物实践

• 发表时间: 2011
• 作者: Fthenakis, George C.;Menzies, Paula
• 通讯作者: Menzies, Paula

RFLP-analysis of polymorphic outer membrane protein loci reveals intraspecies-specific variability among Chlamydophila abortus isolates

多态性外膜蛋白位点的 RFLP 分析揭示了流产衣原体分离株的种内特异性变异

• 作者: Ewan Clark (Author)

Evidence of the association of Chlamydia-like organisms with cases of bovine abortion in the UK

类衣原体生物与英国牛流产病例相关的证据

• 作者: David Longbottom (Author)

Exposure to viral and bacterial pathogens among Soay sheep (Ovis aries) of the St Kilda archipelago.

• DOI: 10.1017/s0950268816000017
• 发表时间: 2016-07
• 期刊: Epidemiology and infection
• 影响因子: 4.2
• 作者: Graham AL;Nussey DH;Lloyd-Smith JO;Longbottom D;Maley M;Pemberton JM;Pilkington JG;Prager KC;Smith L;Watt KA;Wilson K;McNEILLY TN;Brülisauer F
• 通讯作者: Brülisauer F

Profiling antibody responses to infections by Chlamydia abortus enables identification of potential virulence factors and candidates for serodiagnosis.

• DOI: 10.1371/journal.pone.0080310
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Forsbach-Birk V;Foddis C;Simnacher U;Wilkat M;Longbottom D;Walder G;Benesch C;Ganter M;Sachse K;Essig A
• 通讯作者: Essig A