ANTIBIOTIC TRANSPORT IN MYCOBACTERIA INFECTED MACROPHAGE

分枝杆菌感染的巨噬细胞中的抗生素转运

• 批准号: 2076468
• 负责人: THOMAS H STEINBERG
• 金额: $ 15.53万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-15 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2076468
• 关键词: Mycobacterium; acid base balance; antitubercular agents; biological transport; laboratory mouse; macrophage; membrane transport proteins; pharmacokinetics

DESCRIPTION: (Adapted from Applicant's Abstract) Disease caused by Mycobacterium avium and Mycobacterium tuberculosis are major health care problems. These organisms cause intracellular infections, that is, they evade the normal host defenses by residing within the macrophages that would otherwise destroy them. Because of the specialized intracellular environment mycobacteria inhabit, antibiotics must achieve sufficient concentration in this compartment in order to be effective therapeutic agents. The major goal of this proposal to formulate new therapeutic strategies for these infections using modern tools of cell biology to target drugs to the mycobacteria-containing phagosomes. The focus is to characterize one of the cellular systems that influences both the total intracellular accumulation of many drugs and their distribution within the cell:organic anion transporters. One of the several different organic anion transporters mediates secretion of organic anions from the cell. This transporter may influence intracellular antibiotic disposition and may permit achieving adequate concentration of antibiotics in the treatment of intracellular infections. The proposed studies will (1) characterize organic anion transport in phagosomes containing mycobacteria; (2) measure the effect of mycobacteria infection of macrophages on the accumulation and subcellular localization of relevant antibiotics; (3) investigate the role of transmembrane pH gradients in these transport processes and (4) identify the plasma membrane proteins responsible for organic anion transport in these cells.

描述：（改编自申请人摘要） 鸟分枝杆菌和结核分枝杆菌是主要的卫生保健 问题 这些微生物引起细胞内感染，也就是说，它们 通过驻留在巨噬细胞内逃避正常的宿主防御， 否则就会摧毁它们。 由于细胞内的特殊化， 环境分枝杆菌栖息，抗生素必须达到足够的 浓度在这个隔室中，以便有效治疗 剂.该提案的主要目标是制定新的治疗方案， 利用现代细胞生物学工具， 将药物靶向含分枝杆菌的吞噬体。 重点是 描述一个细胞系统，既影响总的 许多药物在细胞内的蓄积及其在细胞内的分布 细胞：有机阴离子转运蛋白。 几个不同的 有机阴离子转运蛋白介导的分泌的有机阴离子从 cell. 这种转运蛋白可能影响细胞内抗生素 处置，并可能允许实现足够的浓度， 抗生素治疗细胞内感染。 拟议 研究将（1）表征吞噬体中有机阴离子的转运 含有分枝杆菌;（2）测量分枝杆菌的作用 巨噬细胞对聚集和亚细胞的感染 相关抗生素的定位;（3）研究 跨膜pH梯度在这些运输过程和（4）确定 负责有机阴离子转运的质膜蛋白 这些细胞。