Evaluation of Mycobacterium smegmatis as a possible surrogate screen for selecting molecules active against multi-drug resistant Mycobacterium tuberculosis
Evaluation of Mycobacterium smegmatis as a possible surrogate screen for selecting molecules active against multi-drug resistant Mycobacterium tuberculosis
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DOI：
10.2323/jgam.53.333
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发表时间：
2007-12-01
影响因子：
1.2
通讯作者：
Sinha, Sudhir
中科院分区：
文献类型：
--
作者：
Chaturvedi, Vinita;Dwivedi, Namrata;Sinha, Sudhir
治疗结核病（TB），特别是耐多药（MDR）疾病需要新的、更好的药物。然而，耐多药结核分枝杆菌的高度传染性限制了其用于大规模筛选可能的候选药物。我们评估了基于“快速生长”分枝杆菌筛选的潜力，以筛选出可能对耐多药结核分枝杆菌具有活性的化合物。测定了耻垢分枝杆菌、草分枝杆菌和偶发分枝杆菌以及结核分枝杆菌的耐多药临床分离株针对抗结核药物异烟肼和利福平的敏感性。在三个快速生长者中，耻垢分枝杆菌被发现表现出与耐多药结核分枝杆菌相似的特征。随后，我们评估了耻垢分枝杆菌作为 120 种合成抗结核活性化合物的“替代”筛选的性能。其中 50 个分子对结核分枝杆菌 H(37)Rv 具有活性，最低抑制浓度 (MIC) 截止值为
New and better drugs are needed for tuberculosis (TB), particularly for the multi-drug resistant (MDR) disease. However, the highly infectious nature of MDR Mycobacterium tuberculosis restricts its use for large scale screening of probable drug candidates. We have evaluated the potential of a screen based on a 'fast grower' mycobacterium to shortlist compounds which could be active against MDR M. tuberculosis. Sensitivity profiles of M. smegmatis, M. phlei and M. fortuitum as well as MDR clinical isolates of M. tuberculosis were determined against anti-TB drugs isoniazid and rifampicin. Among the three fast growers, M. smegmatis was found to display a profile similar to MDR M. tuberculosis. Subsequently we evaluated the performance of M. smegmatis as a 'surrogate' screen for 120 compounds which were synthesized for anti-TB activity. Fifty of these molecules were active against M. tuberculosis H(37)Rv at a minimum inhibitory concentration (MIC) cutoff of