The Journal of General and Applied Microbiology
Online ISSN : 1349-8037
Print ISSN : 0022-1260
ISSN-L : 0022-1260
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Evaluation of Mycobacterium smegmatis as a possible surrogate screen for selecting molecules active against multi-drug resistant Mycobacterium tuberculosis
Vinita ChaturvediNamrata DwivediRama P. TripathiSudhir Sinha
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2007 Volume 53 Issue 6 Pages 333-337

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Abstract

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.

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© 2007 by The Applied Microbiology, Molecular and Cellular Biosciences Research Foundation
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