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

新型质粒携带禽流产衣原体菌株 84/2334 的生物学和病理学特征

• 批准号: BB/X016692/1
• 负责人: David Longbottom
• 金额: $ 131.57万
• 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: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX016692%2F1
• 关键词: Biological; pathological; characterisation; novel; plasmid

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.

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。绵羊地方性流产（OEA）是由革兰氏阴性细菌流产衣原体（Chlamydia abortus）引起的一种具有世界范围内重要经济意义的小反刍动物地方性疾病。在英国，它是绵羊感染性流产的最常见原因，导致妊娠最后2-3周的胎儿死亡或分娩出虚弱的后代，并导致羊群损失高达30%左右。据估计，英国每年的损失约为2500万英镑。这种生物还可以感染人类，导致自然流产，感染可能危及生命。疫苗接种目前被认为是控制疾病最有效的方法，基于灭活或活的整个生物体的疫苗在商业上可用于小反刍动物。然而，据报道，活疫苗在一些动物中引起感染和疾病，而灭活疫苗在保护动物免受感染方面的效力要低得多。因此，有必要开发用于牲畜的更安全、更有效的疫苗。减少动物感染和疾病负担也将减少人类感染的风险。近年来，研究已经进展到开发操纵人类衣原体物种基因组的方法，利用许多菌株拥有的内源性质粒（染色体上存在的DNA之外的DNA）。这些质粒也存在于禽类衣原体物种（鹦鹉热衣原体）中，而abortus就是由衣原体进化而来。然而，到目前为止还没有在C. abortus菌株中发现质粒。最近，我们描述了一种新的菌株的基因组，命名为84/2334，该菌株已被重新分类为C.鹦鹉和C. abortus，并携带一个质粒。因此，该菌株有可能用于开发新的产弧菌疫苗来控制OEA。然而，在此之前，我们需要知道该菌株与C. abortus的生物学相似性，并确定该菌株是否引起与C. abortus相似的感染和疾病。在本项目中，我们将比较84/2334菌株与C. abortus和C. psittaci的生长动态，研究其在靶宿主细胞中的生长周期，确定其致病的关键分子，并确定其引起感染和流产的潜力。这些研究将确定该菌株是否更类似于经典的C. abortus而不是C.鹦鹉螺，并确定其在未来疫苗开发研究中的适用性。