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）是小反刍动物中具有全球意义的经济上重要的地方病。种，由革兰氏阴性细菌流产衣原体引起，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 周内胎儿死亡或产下体弱的后代。据估计，英国每年的损失高达 2500 万英镑左右，这种微生物还可以感染人类，导致自然流产，目前认为接种疫苗可能会危及生命。控制疾病的最有效方法是基于灭活或活的完整生物体的疫苗可用于小型反刍动物，但是，据报道活疫苗会在某些动物中引起感染和疾病，而灭活疫苗也被发现具有这种作用。保护动物免受感染的效果要低得多，因此，需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。开发了操纵人类衣原体物种基因组的方法，利用许多菌株所拥有的内源质粒（染色体上存在的额外DNA），这些质粒也存在于鸟类衣原体物种中。然而，迄今为止，在流产衣原体菌株中尚未发现质粒，该菌株被命名为 84/2334，该菌株已从衣原体中重新分类。因此，该菌株有可能用于开发一种新的流产衣原体疫苗来控制 OEA。了解该菌株与流产梭菌在生物学上的相似程度，并确定该菌株是否引起与流产梭菌相似的感染和疾病。在本项目中，我们将比较 84/2334 菌株与流产梭菌的生长动态。流产和鹦鹉热衣原体，其在目标宿主细胞中的生长周期，识别引起发病机制的关键分子，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与经典衣原体更相似。流产菌与鹦鹉热衣原体相比，并确定其在未来疫苗开发研究中的适用性。