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.read more
Citations
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Journal ArticleDOI
Efflux-Mediated Drug Resistance in Bacteria
Xian-Zhi Li,Hiroshi Nikaido +1 more
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,Hiroshi Nikaido +1 more
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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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
Xian-Zhi Li,Hiroshi Nikaido +1 more
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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