Evaluation of Mycobacterium smegmatis as a possible surrogate screen for selecting molecules active against multi-drug resistant Mycobacterium tuberculosis

The Journal of General and Applied Microbiology

Namrata Dwivedi²  Rama P. Tripathi²  Vinita Chaturvedi¹  Sudhir Sinha¹ 

[1] Drug Target Discovery and Development Division, Central Drug Research Institute;Medicinal and Process Chemistry Division, Central Drug Research Institute

关键词: multi-drug resistance;    Mycobacterium smegmatis;    Mycobacterium tuberculosis;    TB drug development;   

DOI  :  10.2323/jgam.53.333

学科分类：微生物学和免疫学

来源: Applied Microbiology, Molecular and Cellulrar Biosciences Research Foundation

【 摘 要 】

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 H37Rv at a minimum inhibitory concentration (MIC) cutoff of ≤12.50 μg/ml. The M. smegmatis based screen showed 100% specificity and 78% sensitivity vis-à-vis MDR M. tuberculosis. These results highlight the utility of M. smegmatis as a primary screen to shortlist compounds for advanced screening against MDR M. tuberculosis.

【 授权许可】

Unknown