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

J Antibiot (Tokyo). 2020 Nov;73(11):780-789. doi: 10.1038/s41429-020-0320-7. Epub 2020 May 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • DNA-Directed RNA Polymerases / genetics
  • Drug Discovery / methods
  • Drug Evaluation / methods*
  • Drug Resistance, Bacterial
  • Genes, Bacterial / genetics
  • Microbial Sensitivity Tests
  • Mycobacterium smegmatis / drug effects*
  • Mycobacterium smegmatis / genetics
  • Mycobacterium tuberculosis / drug effects*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Alignment
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • RNA, Ribosomal, 16S
  • DNA-Directed RNA Polymerases