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Improved Brucella Vaccine Strains

改进的布鲁氏菌疫苗株

基本信息

批准号：
7540374
负责人：
THOMAS A FICHT
金额：
$ 34.65万
依托单位：
TEXAS A&M AGRILIFE RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2011-12-31
项目状态：
已结题

项目摘要

O-polysaccharide is both the dominant immunogen and a major virulence determinant of Brucella spp. In the absence of O-polysaccharide classical Brucella species do not cause disease, and are rapidly cleared from :he host. Data from in vitro model systems appears less decisive. Although most evidence suggests rough mutants retain resistance to macrophage microbicidal killing mechanisms, some results suggest considerable replicative ability that may be masked by increased sensitivity to early killing mechanisms. However, there are also reports of cytotoxic cell death (CCD) induced by infection with rough mutants that is specific for "nacrophages. CCD is accompanied by elevated levels of tumor necrosis factor (TNFa), and nitric oxide (NO) and examination of macrophages revealed nuclear recruitment of nuclear factor kappa B (NF-kappaB) in macrophages exposed to rough organisms that remained in the cytoplasm of cells infected with smooth organisms. There is an increasing consensus that interaction between Brucella and the host cell may be in part controlled or altered by lipopolysaccharide (LPS) on the surface of Brucella. Our long-range goal is to identify the genes required for intracellular survival of Brucella. The objectives of !his application are to determine the contribution of O-polysaccharide in establishing a successful infection through its interaction with macrophages. Our central hypothesis is that O-polysaccharide is an essential element in the interaction between Brucella and host macrophages and enhances survival by evading or altering the innate immune response. The rationale for the proposed research is that understanding the interactions between smooth organisms and the host cell to elicit proper uptake and survival will enhance understanding of the mechanisms resulting in persistence and disease and provide information for the development of improved vaccines or treatments to enhance clearance of infections. We are particularly well prepared to study this interaction because we have established a Brucella mefitensis mutant bank and in vitro and in vivo models of infection and have the capacity to examine Brucella macrophage interaction at the cellular level and in animals models of infection using molecular, genomic and bioinformatic approaches.

O-多糖是布鲁氏菌的优势免疫原，也是布鲁氏菌的主要毒力决定因子。在缺乏O-多糖的情况下，经典的布鲁氏菌不会引起疾病，并迅速从宿主中清除。来自体外模型系统的数据似乎不那么具有决定性。虽然大多数证据表明粗糙突变体保留巨噬细胞杀微生物剂的杀伤机制的阻力，一些结果表明相当大的复制能力，可能被掩盖的敏感性增加早期杀伤机制。然而，也有报告称，感染了对“那克罗塞”特异的粗糙突变体后，细胞毒性细胞死亡（CCD）会被诱导。CCD伴随着肿瘤坏死因子（TNF α）和一氧化氮（NO）水平的升高，并且巨噬细胞的检查揭示了暴露于粗糙生物体的巨噬细胞中核因子κ B（NF-κ B）的核募集，其保留在被光滑生物体感染的细胞的细胞质中。越来越多的人认为布鲁氏菌与宿主细胞之间的相互作用可能部分受到布鲁氏菌表面脂多糖（LPS）的控制或改变。我们的长期目标是确定布鲁氏菌细胞内生存所需的基因。的目标！他的应用是确定O-多糖在通过其与巨噬细胞的相互作用建立成功感染中的贡献。我们的中心假设是，O-多糖是布鲁氏菌和宿主巨噬细胞之间相互作用的基本要素，并通过逃避或改变先天免疫应答来提高存活率。拟议研究的基本原理是，了解光滑生物体和宿主细胞之间的相互作用，以引起适当的吸收和存活，将增强对导致持久性和疾病的机制的理解，并为开发改进的疫苗或治疗方法提供信息，以提高感染的清除率。我们特别好我们准备研究这种相互作用，因为我们已经建立了一个梅菲布鲁氏菌突变体库和体外和体内感染模型，并有能力在细胞水平和动物感染模型中使用分子，基因组和生物信息学方法来检查布鲁氏菌巨噬细胞相互作用。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Brucellosis: the case for live, attenuated vaccines.

DOI：
10.1016/j.vaccine.2009.08.058
发表时间：
2009-11-05
期刊：
Vaccine
影响因子：
5.5
作者：
Ficht TA;Kahl-McDonagh MM;Arenas-Gamboa AM;Rice-Ficht AC
通讯作者：
Rice-Ficht AC

The Case for Live Attenuated Vaccines against the Neglected Zoonotic Diseases Brucellosis and Bovine Tuberculosis.

现场活疫苗针对被忽视的人畜共患病和牛结核病的病例。

DOI：
10.1371/journal.pntd.0004572
发表时间：
2016-08
期刊：
PLoS neglected tropical diseases
影响因子：
3.8
作者：
Pandey A;Cabello A;Akoolo L;Rice-Ficht A;Arenas-Gamboa A;McMurray D;Ficht TA;de Figueiredo P
通讯作者：
de Figueiredo P

Brucella melitensis VjbR and C12-HSL regulons: contributions of the N-dodecanoyl homoserine lactone signaling molecule and LuxR homologue VjbR to gene expression.