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.

许多传染病会影响牲畜，不仅影响了动物的健康和福利，还影响了农业部门的经济可持续性和未来的粮食安全。卵巢Enzootic流产（OEA）是由革兰氏阴性细菌造成的小型反刍动物中全球意义上重要的内在疾病。在英国，这是绵羊传染性流产的最常见原因，导致怀孕的最后2-3周导致胎儿死亡，或者递送后代弱的后代并造成损失，最高约为30％。估计在英国的损失约为每年2500万英镑。生物体还会感染引起赞助堕胎的人，其中感染可能会危及生命。目前，疫苗接种被认为是控制疾病的最有效方法，基于失活或活机的疫苗可用于小型反刍动物中。然而，据报道，活疫苗会引起某些动物的感染和疾病，并且发现被灭活的疫苗在保护动物免受感染的影响方面有效得多。这是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燃烧也将降低人类感染的风险。近年来，研究已经发展为开发操纵人衣原体物种的基因组的方法，利用许多菌株拥有的内源性质粒（染色体上存在的DNA）（在染色体上存在的DNA）。这些质粒也存在于禽藻（Chlamydia psittaci）中。但是，在堕胎梭菌菌株中尚未发现质粒。最近，我们表征了一种新型菌株的基因组，该菌株被指定为84/2334，该菌株已从C. psittaci重新分类为Aptaci，并携带质粒。因此，该菌株有可能用于开发一种用于控制OEA的新型流产梭菌疫苗。但是，在这样做之前，我们需要知道生物学上的菌株与堕胎梭菌是如何相似的，并确定菌株是否引起感染和疾病是否类似于堕胎梭菌引起的疾病。在这个项目中，我们将比较与肥大孢菌和psittaci相关的84/2334菌株的生长动力学，研究其在靶宿主细胞中的生长周期，确定引起发病机理所涉及的关键分子，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的堕胎梭菌更相似，而不是对psittaci的菌梭菌，并确定其在未来的疫苗开发研究中使用的适用性。