Comparative adherence of bovine and ovine Mannheimia haemolytica strains to air interface respiratory organ cultures models from cattle and sheep
牛和羊溶血曼海姆氏菌菌株对牛和羊空气界面呼吸器官培养模型的比较依从性
基本信息
- 批准号:BB/D018021/1
- 负责人:
- 金额:$ 30.59万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2007
- 资助国家:英国
- 起止时间:2007 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Mannheimia haemolytica is responsible for important respiratory tract infections of cattle and sheep. These infections have a major impact on animal health and cause considerable economic losses to the farming industry in the UK and globally. Antibiotics and vaccines are used to combat these infections but better methods of control are required because the incidence of antibiotic resistant strains is increasing and vaccines do not provide complete protection. The development of more efficient vaccines against M. haemolytica is urgently required but the mechanisms of pathogenesis of this pathogen are poorly understood and protective antigens are ill-defined. M. haemolytica consists of genetically distinct sub-populations that are specifically adapted to, and cause disease in, either cattle or sheep. Furthermore, bovine and ovine isolates have very different forms of a cell-surface protein (OmpA) which, in other bacterial species, is involved in adherence. These data suggest that the OmpA protein of M. haemolytica might be involved in adherence to the upper respiratory tract (URT) of cattle and sheep and play a role in host-adaptation. Pathogenic bacteria possess a wide range of virulence mechanisms but adherence to mucosal surfaces is the first critical stage in the disease process. If adherence can be blocked it should, in theory, be possible to prevent colonisation and progression to disease. Unfortunately, very little is known about the mechanisms used by M. haemolytica to adhere to the URT of cattle and sheep. A major reason for this is the unavailability of suitable laboratory methods that represent the tissues and physiological conditions of the bovine and ovine URT. It is very difficult and ethically unjustifiable to carry out experiments in live cattle and sheep. Recently, air-interface respiratory organ culture methods have been developed in other species which use tissue derived from the URT of dead animals and physiological conditions that are similar to those encountered in the living animal. This project proposes to use this technology to investigate the adherence of bovine and ovine M. haemolytica isolates to the URT of cattle and sheep and to study the role of OmpA in adherence and host-specificity. The specific aims and objectives of the project are as follows: (1) To characterise in detail the interactions between M. haemolytica and respiratory epithelium by using bovine and ovine air-interface respiratory organ culture models to investigate bacterial adherence and colonisation of the URT of cattle and sheep. Air-interface cultures will be established using tissue from different regions of the URT including the nasal cavity (turbinates), the nasopharynx (tonsils), and trachea and infected with a well-characterised pathogenic bovine and ovine field isolate. (2) To study the adherence of bovine and ovine M. haemolytica isolates to organ culture models representing different regions of the URT of cattle and sheep. In this way we will determine whether adherence of bovine and ovine M. haemolytica isolates to the URT occurs in a host-specific manner and contributes to host adaptation in this species. (3) To evaluate the role of the OmpA protein in the adherence of bovine and ovine M. haemolytica isolates to organ culture models of cattle and sheep. In this way we will test the hypothesis that OmpA has a ligand-like function, is involved in binding in a host-specific manner to the bovine and ovine URT, and plays a role in colonisation and host-specificity. The air-interface respiratory organ culture models developed during the course of the project have significant potential applications in the study of other pathogens of cattle and sheep. Therefore, the proposed project will lead to the more rapid progression not only of M. haemolytica research but also research in related fields. The wider use of these models will lead to a significant reduction in the use of cattle and sheep in animal experiments.
溶血性曼氏菌是引起牛和羊呼吸道感染的重要病原菌。这些感染对动物健康产生重大影响,并对英国和全球的农业造成相当大的经济损失。抗生素和疫苗用于对抗这些感染,但需要更好的控制方法,因为抗生素耐药菌株的发生率正在增加,疫苗不能提供完全的保护。因此,研制更有效的抗M.溶血性病原体是迫切需要的,但这种病原体的发病机制知之甚少,保护性抗原是不明确的。M.溶血性链球菌由遗传上不同的亚群组成,这些亚群特别适应牛或羊并在牛或羊中引起疾病。此外,牛和绵羊分离物具有非常不同形式的细胞表面蛋白(OmpA),在其他细菌物种中,OmpA参与粘附。这些数据表明,M.溶血性弧菌可能参与牛和绵羊上呼吸道(URT)的粘附,并在宿主适应中发挥作用。病原菌具有广泛的毒力机制,但粘附于粘膜表面是疾病过程中的第一个关键阶段。如果可以阻断粘附,理论上应该可以防止定植和疾病进展。不幸的是,人们对M使用的机制知之甚少。溶血菌粘附在牛和羊的URT上。其主要原因是无法获得代表牛和绵羊URT组织和生理条件的合适实验室方法。在活的牛羊身上进行实验是非常困难的,在伦理上也是不合理的。最近,在其他物种中开发了空气界面呼吸器官培养方法,其使用来自死亡动物的URT的组织和与活动物中遇到的生理条件相似的生理条件。本项目拟利用该技术研究牛、羊M.溶血性弧菌分离株的URT的牛和羊,并研究的作用,OmpA的粘附和主机的特异性。本研究的具体目标和目的如下:(1)详细研究M。溶血性和呼吸道上皮通过使用牛和绵羊空气界面呼吸器官培养模型来研究牛和绵羊URT的细菌粘附和定殖。将使用来自URT不同区域(包括鼻腔(鼻甲)、鼻咽(扁桃体)和气管)的组织建立空气界面培养物,并使用充分表征的致病性牛和绵羊田间分离株进行感染。(2)研究牛、羊M.溶血性弧菌分离株与代表牛和羊URT不同区域的器官培养模型。用这种方法我们将确定牛和羊M.溶血性弧菌分离株对URT的耐受性以宿主特异性方式发生,并有助于该种属的宿主适应。(3)目的探讨OmpA蛋白在牛、羊支原体粘附中的作用。溶血性弧菌分离株的牛和羊的器官培养模型。以这种方式,我们将测试的假设,OmpA具有配体样功能,参与结合在一个主机特异性的方式,牛和羊的URT,并在殖民和主机特异性发挥作用。在该项目过程中开发的空气界面呼吸器官培养模型在牛和羊的其他病原体研究中具有重要的潜在应用。因此,拟议的项目将导致更快的发展,不仅M。溶血性研究以及相关领域的研究。这些模型的广泛使用将导致动物实验中牛和羊的使用大幅减少。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
International Pasteurellaceae Society Conference - abstract 1
国际巴斯德氏菌协会会议 - 摘要 1
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:Josh Slater (Author)
- 通讯作者:Josh Slater (Author)
International Pasteurellaceae Society Conference - abstract 2
国际巴斯德氏菌协会会议 - 摘要 2
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:Jonathan D A Hounsome (Author)
- 通讯作者:Jonathan D A Hounsome (Author)
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Josh Slater其他文献
Josh Slater的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Limiting effects of a tick kunitz protease inhibitor on rickettsial infection
蜱库尼兹蛋白酶抑制剂对立克次体感染的限制作用
- 批准号:
7741122 - 财政年份:2011
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
8070101 - 财政年份:2010
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
7846689 - 财政年份:2009
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
7921274 - 财政年份:2009
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
8100485 - 财政年份:2007
- 资助金额:
$ 30.59万 - 项目类别:
Comparative adherence of bovine and ovine Mannheimia haemolytica strains to air-interface respiratory organ culture models from cattle and sheep
牛和羊溶血曼海姆氏菌菌株对牛和羊空气界面呼吸器官培养模型的比较依从性
- 批准号:
BB/D018137/1 - 财政年份:2007
- 资助金额:
$ 30.59万 - 项目类别:
Research Grant
The roles of Anaplasma phagocytophilum surface proteins in infection
嗜吞噬细胞无形体表面蛋白在感染中的作用
- 批准号:
9377350 - 财政年份:2007
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
7558793 - 财政年份:2007
- 资助金额:
$ 30.59万 - 项目类别:
Characterization of Anaplasma phagocytophilum adhesins
嗜吞噬细胞粘附素无形体的表征
- 批准号:
7636815 - 财政年份:2007
- 资助金额:
$ 30.59万 - 项目类别: