Application of Mycobacterium smegmatis as a surrogate to evaluate drug leads against Mycobacterium tuberculosis

Abstract

Discovery of new anti-tuberculosis (TB) drugs is a time-consuming process due to the slow-growing nature of Mycobacterium tuberculosis (Mtb). A requirement of biosafety level 3 (BSL-3) facility for performing research associated with Mtb is another limitation for the development of TB drug discovery. In our screening of BSL-1 Mycobacterium spp. against a battery of TB drugs, M. smegmatis (ATCC607) exhibits good agreement with its drug susceptibility against the TB drugs under a low-nutrient culture medium (0.5% Tween 80 in Middlebrook 7H9 broth). M. smegmatis (ATCC607) enters its dormant form in 14 days under a nutrient-deficient condition (a PBS buffer), and shows resistance to a majority of TB drugs, but shows susceptibility to amikacin, capreomycin, ethambutol, and rifampicin (with high concentrations) whose activities against non-replicating (or dormant) Mtb were previously validated.

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Acknowledgements

The National Institutes of Health is greatly acknowledged for financial support of this work (Grant GM114611). MK thanks UTRF (University of Tennessee Health Science Center) for generous financial support (Innovation award R079700292). NMR data were obtained on instruments supported by the NIH Shared Instrumentation Grant. The following reagent was obtained through BEI Resources, NIAID, NIH: Mycobacterium tuberculosis, Strain H37Rv. JY thanks the support of Cystic Fibrosis Foundation Award (JI1810). This article is dedicated to the memory of Dr Isao Kitagawa, Professor Emeritus of pharmaceutical sciences at Osaka University, an inspirational scientist.

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Lelovic, N., Mitachi, K., Yang, J. et al. Application of Mycobacterium smegmatis as a surrogate to evaluate drug leads against Mycobacterium tuberculosis. J Antibiot (2020). https://doi.org/10.1038/s41429-020-0320-7

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