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Molecular Mechanisms of Drug Tolerance in Mycobacterium tuberculosis

Authors
  • Antonova, A. V.
  • Gryadunov, D. A.
  • Zimenkov, D. V.
Type
Published Article
Journal
Molecular Biology
Publisher
Pleiades Publishing
Publication Date
May 01, 2018
Volume
52
Issue
3
Pages
372–384
Identifiers
DOI: 10.1134/S0026893318030020
Source
Springer Nature
Keywords
License
Yellow

Abstract

A dramatic increase in drug-resistant forms of tuberculosis (TB) stimulates a search for novel anti- TB drugs and studies of the drug resistance acquisition. One of the possible causes is a phenotypic resistance or drug tolerance which is not associated with genomic changes. The majority of anti-TB drugs eliminate 99% of MTB cells in 3–5 days, but the remaining subpopulation becomes unsusceptible to treatment and capable for long-term persistence with ability to resuscitate once the external adverse factor is removed. This evasion of the stress factor facilitates selection of resistant forms, thus warranting long-term treatment with at least four antibacterial drugs in TB. The review considers the main mechanisms of bacterial tolerance that are due to alterations in the cell wall, activation of efflux pumps, induction of transcriptional regulons, changes in metabolic flows, and modification of molecular machineries.

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