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Open AccessJournal ArticleDOI

Role of mycobacterial efflux transporters in drug resistance: an unresolved question

TLDR
This review highlights recent advances in the understanding of efflux-mediated drug resistance in mycobacteria, including the distribution of Efflux systems in these organisms, their substrate profiles and their contribution to drug resistance.
Abstract
Two mechanisms are thought to be involved in the natural drug resistance of mycobacteria: the mycobacterial cell wall permeability barrier and active multidrug efflux pumps. Genes encoding drug efflux transporters have been isolated from several mycobacterial species. These proteins transport tetracycline, fluoroquinolones, aminoglycosides and other compounds. Recent reports have suggested that efflux pumps may also be involved in transporting isoniazid, one of the main drugs used to treat tuberculosis. This review highlights recent advances in our understanding of efflux-mediated drug resistance in mycobacteria, including the distribution of efflux systems in these organisms, their substrate profiles and their contribution to drug resistance. The balance between the drug transport into the cell and drug efflux is not yet clearly understood, and further studies are required in mycobacteria.

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Citations
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Journal ArticleDOI

Efflux-Mediated Drug Resistance in Bacteria

TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
Journal ArticleDOI

Efflux-mediated antimicrobial resistance

TL;DR: Given the clinical significance of multidrug (and drug-specific) exporters, efflux must be considered in formulating strategies/approaches to treating drug-resistant infections, both in the development of new agents less impacted by efflux and in targeting efflux directly with efflux inhibitors.
Journal ArticleDOI

Efflux-mediated drug resistance in bacteria: an update.

Xian-Zhi Li, +1 more
- 20 Aug 2009 - 
TL;DR: The multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.
Journal ArticleDOI

Mycobacterium abscessus: a new antibiotic nightmare

TL;DR: A review of previous and recent findings on the resistance of M. abscessus to antibiotics highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance and raises the profile of this important pathogen.
Journal ArticleDOI

Bacterial efflux pump inhibitors from natural sources

TL;DR: The use of bacterial resistance modifiers such as EPIs could facilitate the re-introduction of therapeutically ineffective antibiotics back into clinical use such as ciprofloxacin and might even suppress the emergence of MDR strains.
References
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Journal ArticleDOI

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

TL;DR: Changing the use of tetracyclines in human and animal health as well as in food production is needed if this class of broad-spectrum antimicrobials through the present century is to continue to be used.
Journal Article

The major facilitator superfamily.

TL;DR: Evidence is presented substantiating the proposal that an internal tandem gene duplication event gave rise to a primordial MFS protein before divergence of the family members.
Journal ArticleDOI

Prevention of drug access to bacterial targets: permeability barriers and active efflux

TL;DR: As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.
Journal ArticleDOI

Efflux-Mediated Drug Resistance in Bacteria

TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
Journal ArticleDOI

Crystal structure of bacterial multidrug efflux transporter AcrB

TL;DR: In this article, the crystal structure of AcrB at 3.5 A resolution was determined, which implies that substrates translocated from the cell interior through the transmembrane region and from the periplasm through the vestibules are collected in the central cavity and then actively transported through the pore into the TolC tunnel.
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