Vol 52(2018) N 3 p. 372-384; DOI 10.1134/S0026893318030020
A.V. Antonova, D.A. Gryadunov, D.V. Zimenkov*
Molecular Mechanisms of Drug Tolerance in Mycobacterium tuberculosisEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
Received - 2016-11-18; Accepted - 2017-09-25
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.
Mycobacterium tuberculosis, regulation of gene expression, phenotypic resistance, drug tolerance, efflux pumps