Biological and pathological characterisation of novel plasmid-carrying avian Chlamydia abortus strain 84/2334

许多传染病影响牲畜，不仅影响动物的健康和福利，而且影响农业部门的经济可持续性和未来的粮食安全。绵羊流产性流产(OEA)是由革兰氏阴性菌流产衣原体引起的一种在小型反刍动物中具有重要经济意义的世界性地方性疾病。在英国，它是绵羊传染性流产的最常见原因，导致怀孕最后2-3周的胎儿死亡或分娩虚弱的后代，造成高达30%的羊群损失。据估计，英国每年的损失约为2500万英镑。这种微生物还可以感染导致自然流产的人类，在人类中感染可能危及生命。疫苗接种目前被认为是控制疾病的最有效方式，基于灭活或活的整个生物体的疫苗可在商业上用于小型反刍动物。然而，据报道，活疫苗会在一些动物中引起感染和疾病，灭活疫苗在保护动物免受感染方面的有效性要低得多。因此，有必要开发用于牲畜的更安全、更有效的疫苗。减少动物的感染和疾病负担也将降低人类感染的风险。近年来，研究已经发展到利用许多衣原体菌株拥有的内源性质粒(染色体上存在的DNA之外的DNA)来操纵人类衣原体物种基因组的方法。这些质粒也存在于鸟类衣原体物种(鹦鹉热衣原体)中，流产衣原体就是从这些物种进化而来的。然而，到目前为止，还没有在流产梭菌菌株中发现质粒。最近，我们对一株新菌株的基因组进行了鉴定，命名为84/2334，该菌株已从鹦鹉热菌重新分类为流产弧菌，并携带一个质粒。因此，该菌株有可能被用来开发一种新的控制OEA的流产线虫疫苗。然而，在做这项工作之前，我们需要知道该菌株在生物学上与流产弧菌有多相似，并确定该菌株是否会引起与堕胎弧菌类似的感染和疾病。在本项目中，我们将比较84/2334菌株与流产弧菌和鹦鹉热杆菌的生长动力学，研究其在目标宿主细胞中的生长周期，确定与致病相关的关键分子，并确定其引起感染和流产的可能性。这些研究将确定该菌株是否与经典流产弧菌更相似，而不是鹦鹉热弧菌，并确定其是否适合用于未来的疫苗开发研究。

Many infectious diseases affect livestock, impacting not only on the health and welfare of the animals but also on the economic sustainability of the agricultural sector and future food security. Ovine enzootic abortion (OEA) is an economically important endemic disease of worldwide significance in small ruminant species, caused by the Gram-negative bacterium Chlamydia abortus. In the UK it is the most common cause of infectious abortion in sheep, resulting in foetal death in the last 2-3 weeks of pregnancy or the delivery of weak offspring and causing losses in a flock of up to around 30%. Losses in the UK have been estimated to be around £25M per annum. The organism can also infect humans causing spontaneous abortion, and in whom infections can be life-threatening. Vaccination is currently considered the most effective way of controlling disease and vaccines based on inactivated or live whole-organisms are commercially available for use in small ruminants. However, live vaccines have been reported to cause infection and disease in some animals and inactivated vaccines have been found to have much lower effectiveness in protecting animals from infections. Thus, there is a need to develop safer, more effective vaccines for use in livestock. Reducing infection and disease burden in animals will also reduce the risk of infections in humans. In recent years, research has progressed into developing methods for manipulating the genomes of human chlamydial species, making use of an endogenous plasmid (DNA that is extra to that present on the chromosome) that many of the strains possess. These plasmids are also present in avian chlamydial species (Chlamydia psittaci) from which C. abortus evolved. However, no plasmid has been found to date in C. abortus strains. Recently, we have characterised the genome of a novel strain, designated 84/2334, which has been reclassified from C. psittaci to C. abortus and carries a plasmid. Therefore, this strain could potentially be used to develop a new C. abortus vaccine for controlling OEA. However, before doing this, we need to know how biologically similar the strain is to C. abortus and determine whether the strain causes infection and disease similar to that caused by C. abortus. In this project we will compare the growth dynamics of the 84/2334 strain in relation to both C. abortus and C. psittaci, investigate its growth cycle in the target host cell, identify the key molecules involved in causing pathogenesis, and determine its potential to cause infection and abortion. These studies will identify whether the strain is more similar to classical C. abortus than to C. psittaci and determine its suitability for use in future vaccine development studies.