Jacobs W R, Barletta R G, Udani R, Chan J, Kalkut G, Sosne G, Kieser T, Sarkis G J, Hatfull G F, Bloom B R
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Science. 1993 May 7;260(5109):819-22. doi: 10.1126/science.8484123.
Effective chemotherapy of tuberculosis requires rapid assessment of drug sensitivity because of the emergence of multidrug-resistant Mycobacterium tuberculosis. Drug susceptibility was assessed by a simple method based on the efficient production of photons by viable mycobacteria infected with specific reporter phages expressing the firefly luciferase gene. Light production was dependent on phage infection, expression of the luciferase gene, and the level of cellular adenosine triphosphate. Signals could be detected within minutes after infection of virulent M. tuberculosis with reporter phages. Culture of conventional strains with antituberculosis drugs, including isoniazid or rifampicin, resulted in extinction of light production. In contrast, light signals after luciferase reporter phage infection of drug-resistant strains continued to be produced. Luciferase reporter phages may help to reduce the time required for establishing antibiotic sensitivity of M. tuberculosis strains from weeks to days and to accelerate screening for new antituberculosis drugs.
由于多重耐药结核分枝杆菌的出现，有效的结核病化疗需要快速评估药物敏感性。通过一种基于感染表达萤火虫荧光素酶基因的特定报告噬菌体的活分枝杆菌高效产生光子的简单方法来评估药物敏感性。发光依赖于噬菌体感染、荧光素酶基因的表达以及细胞三磷酸腺苷的水平。在用报告噬菌体感染强毒结核分枝杆菌后几分钟内就能检测到信号。用包括异烟肼或利福平在内的抗结核药物培养传统菌株会导致发光消失。相比之下，耐药菌株在荧光素酶报告噬菌体感染后仍会持续产生光信号。荧光素酶报告噬菌体可能有助于将确定结核分枝杆菌菌株抗生素敏感性所需的时间从数周缩短至数天，并加速新型抗结核药物的筛选。
