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Review
. 2017 Oct 13:10:333-342.
doi: 10.2147/IDR.S144446. eCollection 2017.

Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis

Mashael Al-Saeedi  1 , Sahal Al-Hajoj  1
Affiliations
Review

Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis

Mashael Al-Saeedi et al. Infect Drug Resist. .

Erratum in

Abstract

Despite the efficacy of antibiotics to protect humankind against many deadly pathogens, such as Mycobacterium tuberculosis, nothing can prevent the emergence of drug-resistant strains. Several mechanisms facilitate drug resistance in M. tuberculosis including compensatory evolution, epistasis, clonal interference, cell wall integrity, efflux pumps, and target mimicry. In this study, we present recent findings relevant to these mechanisms, which can enable the discovery of new drug targets and subsequent development of novel drugs for treatment of drug-resistant M. tuberculosis.

Keywords: Mycobacterium tuberculosis; antibiotic resistance; compensatory evolution; efflux pumps; epistasis; fitness cost.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Development of drug resistance. Notes: 1, when MTB acquires mutations during therapy, they reduce MTB fitness (clones A and B). 2, an acquired secondary mutation restores MTB fitness. 3, the epistatic interaction between mutations improves MTB fitness and maintains drug resistance within the specific MTB genetic background. 4, clonal interference determines clone fate via competition, which leads to emergence of the most dominate clone with drug resistance in the population and elimination of the clone with a lower mutational effect. Abbreviation: MTB, Mycobacterium tuberculosis.
Figure 2
Figure 2
Forms of epistatic interaction between mutations. Note: (↑) indicated high MTB fitness and (↓) indicated low MTB fitness. Abbreviation: MTB, Mycobacterium tuberculosis.
Figure 3
Figure 3
MTB can exhibit resistance to drugs via: 1, intrinsically decreased permeability of the cell wall; 2, acquisition of mutations that block drug entry; 3, extrusion drugs via efflux pumps; 4, modification of the drug or its target, or 5, target mimicry. Note: Possible drug targets are indicated by red circles. Abbreviations: INH, isoniazid; MTB, Mycobacterium tuberculosis; TB, tuberculosis.
See this image and copyright information in PMC

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