ASSESSMENT OF DRUG RESISTANCE IN MYCOBACTERIUM AVIUM

鸟分枝杆菌的耐药性评估

• 批准号: 3132331
• 负责人: CHARLOTTE M MCCARTHY
• 金额: $ 7.6万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132331
• 关键词: AIDS; Actinomycetales infection; Mycobacterium; aminoacid inhibitor; antibacterial agents; antibiotics; antifungal antibiotics; antimetabolites; antineoplastic antibiotics; antiprotozoal agents; antitubercular agents; azacitidine; bactericidal immunity; clofibrate; combination chemotherapy; drug adverse effect; drug screening /evaluation; ethidium; fluorouracil; glutamates; isoniazid; lipid metabolism; macrophage; microorganism disease chemotherapy; microorganism growth; nitrogen metabolism; nucleic acid metabolism; phenazines; plant extracts; rifamycins; secondary infection; tissue /cell culture; tuberculosis

Mycobacterium avium is an acid-fast bacterium that is ubiquitous in nature; it infects many humans and causes disease in certain individuals. Most patients with disease caused by M. avium have some other underlying disease, such as acquired immunodeficiency syndrome (AIDS). The mycobacterial disease is difficult to treat because of the microbe's innate drug resistance. Certain features most closely associated with the growth and division of M. avium include metabolic and enzyme activities that differ from those found in eucaryote cells, such as host macrophages. The long-term goal is to identify those drugs that will be toxic for M. avium and yet nontoxic for macrophages. The specific aims of this project are to determine the in vitro susceptibility of M. avium to antimetabolites that interfere with lipid, nitrogen, and nucleic acid metabolism. The drugs will be tested individually, and in combination, against M. avium in a defined medium that lacks albumin. Effect on the growth of the bacterium will be determined by turbidity, viability, and isotope incorporation measurements. The concentration of drugs added to the medium will be monitored by chemical and bioassay procedures to ensure that they are not inactivated by the culture conditions. Those drugs or combinations that have activity against M. avium will be tested for nontoxicity to macrophages cultured in vitro.

鸟分枝杆菌是一种自然界中普遍存在的抗酸细菌。 它感染许多人并导致某些人患病。 最多 患有由鸟分枝杆菌引起的疾病的患者还有一些其他潜在的疾病 疾病，例如获得性免疫缺陷综合症（艾滋病）。 这 由于微生物的先天性，分枝杆菌疾病很难治疗 耐药性。 某些特征与 M.的生长和分裂密切相关。 avium 包括与发现的不同的代谢和酶活性 在真核细胞中，例如宿主巨噬细胞。 长期目标是 确定那些对鸟分枝杆菌有毒但对鸟分枝杆菌无毒的药物 巨噬细胞。 该项目的具体目标是确定体外 鸟分枝杆菌对干扰脂质的抗代谢物的敏感性， 氮和核酸代谢。 这些药物将针对鸟分枝杆菌进行单独和联合测试 在缺乏白蛋白的确定培养基中。 对生长的影响 细菌将由浊度、活力和同位素确定 合并测量。 添加到培养基中的药物浓度 将通过化学和生物测定程序进行监测，以确保它们 不会因培养条件而失活。 那些药物或组合 对鸟分枝杆菌具有活性的药物将进行无毒性测试 体外培养的巨噬细胞。