METABOLIC MAINTENANCE & GROWTH OF MYCOBACTERIUM LEPRAE

代谢维持

• 批准号: 3454649
• 负责人: Scott G. Franzblau
• 金额: $ 4.67万
• 依托单位: NATIONAL HANSEN'S DISEASE PROGRAM
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454649
• 关键词: Mycobacterium leprae; acid base balance; adenosine triphosphate; athymic mouse; bacterial antigens; bioassay; carbon; cellular respiration; glycolipids; growth media; laboratory mouse; leprosy; microorganism classification; microorganism culture; microorganism growth; microorganism metabolism; microscopy; oxidation; oxygen tension; palmitates; radionuclides; radiotracer; scintillation counter

Studies will be carried out with inocula of Mycobacterium leprae, freshly harvested, from the infected foot pads of nu/nu mice and enriched for viable organisms, to explore optimal biophysical and nutritional parameters for the metabolic maintenance of the leprosy bacillus using the following combination of sensitive metabolic assays: a) quantitation of intracellular adenosine triphosphate (ATP), b) incorporation of 14C-palmitate into PGL-1, c) measurement of the rate of 14CO2 released from 14C- palmitate. The combined use of these indicators of net energy status, anabolic and catabolic activity will overcome the limitations inherent in using a single metabolic assay. Preliminary studies indicate an acidic pH optimum (5.5-6.5) and a requirement for continuous maintenance of a gaseous environment with an oxygen concentration below ambient (2.5-10%) Metabolic maintenance and in vitro drug susceptibility testing under these conditions are markedly superior to closed systems employing neutral pH. This approach should lead to the step-wise development of a medium which will support long-term maintenance and subsequently genuine growth of M. leprae. Less than total success should still allow significant improvement in an in vitro medium in which drug activity against M. leprae could be assessed via changes in metabolic activity.

将使用麻风分枝杆菌接种物进行研究， 新鲜收获，来自 nu/nu 小鼠受感染的足垫， 富集活生物体，探索最佳的生物物理和 维持代谢的营养参数 麻风杆菌使用以下敏感组合 代谢测定：a) 细胞内腺苷的定量 三磷酸盐 (ATP)，b) 将 14C-棕榈酸酯掺入 PGL-1， c) 测量 14C- 释放 14CO2 的速率 棕榈酸酯。 这些净能量指标的综合运用 状态、合成代谢和分解代谢活动将克服 使用单一代谢测定固有的局限性。 初步研究表明最适 pH 值为酸性 (5.5-6.5)， 持续维持气体环境的要求 氧气浓度低于环境温度 (2.5-10%) 代谢 维持和体外药敏试验在这些 条件明显优于采用封闭系统 中性pH值。 这种方法应该导致逐步 开发一种能够长期支持的媒介 麻风分枝杆菌的维持和随后的真正生长。 较少的 比完全成功仍应允许在 体外培养基，其中针对麻风分枝杆菌的药物活性可能是 通过代谢活动的变化进行评估。

项目成果

In vitro effects of antimicrobial agents on Mycobacterium leprae in mouse peritoneal macrophages.

抗菌药物对小鼠腹膜巨噬细胞中麻风分枝杆菌的体外影响。

• DOI: 10.1128/aac.33.5.657
• 发表时间: 1989
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Ramasesh,N;Krahenbuhl,JL;Hastings,RC
• 通讯作者: Hastings,RC

Fusidic acid is highly active against extracellular and intracellular Mycobacterium leprae.

夫西地酸对细胞外和细胞内麻风分枝杆菌具有高度活性。

• DOI: 10.1128/aac.36.1.92
• 发表时间: 1992
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Franzblau,SG;Biswas,AN;Harris,EB
• 通讯作者: Harris,EB

In vitro activities of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae.

氨基糖苷类、林可酰胺类和利福霉素对麻风分枝杆菌的体外活性。

• DOI: 10.1128/aac.35.6.1232
• 发表时间: 1991
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Franzblau,SG