MYCOBACTERIAL ENVIRONMENT WITHIN MACROPHAGES

巨噬细胞内的分枝杆菌环境

• 批准号: 6511219
• 负责人: Luiz Eduardo Bermudez
• 金额: $ 8.96万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-15 至 2002-07-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511219
• 关键词: Mycobacterium avium; Mycobacterium smegmatis; X ray microscopy; bacterial cytopathogenic effect; calcium; copper; dendritic cells; host organism interaction; human tissue; intracellular parasitism; iron; laboratory mouse; macrophage; magnesium; manganese; phagocytosis; phosphorus; potassium; sulfur; vesicle /vacuole; virulence; zinc

Mycobacterium avium and Mycobacterium tuberculosis are intracellular pathogens that infect mononuclear phagocytes and survive within tissue macrophages. Tuberculosis is responsible for millions of deaths annually, and M. avium is the most common pathogen causing systemic disease in AIDS patients. Both bacteria survive inside membrane-bound vacuoles in macrophages. The intracellular localization of these organisms suggest that they are well adapted for survival in the host and that they probably can obtain sufficient amounts of nutrients inside the host cells. The presence or absence of elements, such as iron, in the environment is known to influence gene expression in bacteria. It has been assumed that macrophage vacuoles are deficient in iron, as a host defense mechanism against infection. Improving our understanding about the environment within the mycobacterial vacuole and how mycobacteria respond to the conditions present in the vacuoles will provide new insights into pathogenic mechanisms. We propose to: (1) Determine the presence and total concentration as well as the available concentration of important elements such as iron, potassium, phosphorus, sulphur, calcium, magnesium, manganese, copper and zinc in M. avium vacuole in macrophages and dentritic cells compared to M. smegmatis vacuoles by using two methods: (a) hard X-ray microscopy, and (b) bacterial reporte systems. (2a) Establishing the role of the environment within mycobacterial vacuoles on the expression of mycobacterial putative virulence determinants; (b) determine the importance of these determinants in virulence. This is the first time that we will be able to obtain data on the concentrations of single elements in mycobacterial phagosomes. We believe that the proposed studies will generate important information about the phagosome environment and the mycobacterial response to it.

分枝杆菌和结核分枝杆菌是感染单核吞噬细胞并在组织巨噬细胞中存活的细胞内病原体。 结核病每年导致数百万人死亡，而鸟杆菌是导致艾滋病患者全身性疾病的最常见病原体。 这两种细菌均在巨噬细胞中膜结合的液泡内生存。这些生物的细胞内定位表明，它们非常适合在宿主中存活，并且可能可以在宿主细胞内获得足够量的营养。 已知在环境中存在或不存在元素（例如铁）会影响细菌中的基因表达。 已经假定巨噬细胞液泡缺乏铁，作为一种反对感染的宿主防御机制。提高我们对分枝杆菌液泡内环境的理解以及分枝杆菌如何应对液泡中的条件，将为致病机制提供新的见解。我们提出：（1）确定重要元素的存在和总浓度以及可用的浓度，例如铁，钾，磷，硫，硫，钙，镁，镁，锰，锰，铜和锌在巨噬细胞中与Smegmatis actial M. referner act act act和（a）相比，在巨噬细胞和可怜的细胞中使用两个方法和（a s s a s a s s a s a s a a vaime）。 （2a）确定环境在分枝杆菌液泡中的作用在分枝杆菌推定的毒力决定因素上的表达中； （b）确定这些决定因素在毒力中的重要性。这是我们第一次能够获取分枝杆菌吞噬体中单个元素浓度的数据。我们认为，拟议的研究将产生有关吞噬体环境和对其分生不清反应的重要信息。