SURFACE PROTEIN ASSOCIATED VIRULENCE OF RHODOCOCCUS

红球菌表面蛋白相关毒力

• 批准号: 2457632
• 负责人: BARBARA A BYRNE
• 金额: $ 6.21万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2457632
• 关键词: Actinomycetales; SCID mouse; bacterial cytopathogenic effect; bacterial pneumonia; bacterial proteins; gene expression; host organism interaction; lung; macrophage; molecular cloning; phenotype; site directed mutagenesis; transfection; virulence

Intracellular pathogens are responsible for many globally important diseases in human beings. The ability to evade the bactericidal activity of the macrophage is key to their survival and multiplication in the mammalian host. Rhodococcus equi is a facultative intracellular pathogen which causes severe granulomatous pneumonia in foals and immunocompromised human beings. R. equi is an important opportunistic pathogen in human patients suffering from the acquired immunodeficiency syndrome (AIDS) as evidenced by the increasing number of reported cases in the last 5 years. Diagnosis of rhodococcal pneumonia can be difficult and may be delayed until the development of advanced disease when treatment is often unsuccessful. Entry and survival within the pulmonary macrophage leads to persistence of this organism in the lung of infected human and equine patients by evasion of host immune responses. Virulent and avirulent R. equi strains have been identified based on their ability to persist within the lung of severe combined immunodeficient (SCID) mice following intratracheal inoculation or by lethal dose 50 determination using immunocompetent mice. Similarly, virulent strains are capable of persisting and multiplying within macrophages in vitro. A 15-17 kDa surface protein (VAP A) is consistently expressed by virulent R. equi but not by avirulent strains leading to its designation as a virulence- associated protein. The close correlation between the virulent phenotype and ability to express this protein indicates that this protein may have an essential role in persistence of R. equi within the lung and macrophages. The goal of this proposal is to determine if VAP A is essential for persistence within the lung of an immunodeficient host and within macrophages in vitro. These hypotheses will be tested by elimination of expression of VAP A by mutagenesis and testing of virulence 1) in vivo and 2) within macrophages in vitro.

细胞内病原体导致许多全球重要的疾病 人类的疾病。逃避杀菌活性的能力 巨噬细胞的生存和增殖的关键 哺乳动物宿主。马红球菌是一种兼性细胞内病原体 这会导致马驹出现严重的肉芽肿性肺炎 免疫功能低下的人类。 R.equi 是一种重要的机会主义者 患有获得性免疫缺陷的人类患者的病原体 报告病例数量的增加证明了艾滋病综合症（艾滋病） 在过去的5年里。红球菌肺炎的诊断可能很困难 并且可能会延迟到发展为晚期疾病时 治疗常常不成功。进入肺内并存活 巨噬细胞导致这种生物体在感染者的肺部持续存在 通过逃避宿主免疫反应而感染人类和马患者。剧毒 和无毒力的马罗氏菌菌株已根据其能力被鉴定 持续存在于严重联合免疫缺陷 (SCID) 小鼠的肺内 气管内接种后或通过致死剂量50测定 使用免疫功能正常的小鼠。同样，强毒菌株能够 在体外的巨噬细胞内持续存在并繁殖。 15-17 kDa 表面蛋白 (VAP A) 始终由有毒的 R. equal 表达，但 不是由无毒菌株导致其被指定为毒力- 相关蛋白。毒力表型之间的密切相关性 表达该蛋白质的能力表明该蛋白质可能具有 马罗氏菌在肺内持续存在的重要作用 巨噬细胞。该提案的目标是确定 VAP A 是否 对于免疫缺陷宿主肺内的持续存在至关重要，并且 体外巨噬细胞内。这些假设将被检验 通过诱变和测试消除 VAP A 的表达 毒力 1) 体内和 2) 体外巨噬细胞内。