Efflux-mediated drug resistance in bacteria: an update.
Xian-Zhi Li,Hiroshi Nikaido +1 more
TLDR
The multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.Abstract:
Drug efflux pumps play a key role in drug resistance and also serve other functions in bacteria. There has been a growing list of multidrug and drug-specific efflux pumps characterized from bacteria of human, animal, plant and environmental origins. These pumps are mostly encoded on the chromosome, although they can also be plasmid-encoded. A previous article in this journal provided a comprehensive review regarding efflux-mediated drug resistance in bacteria. In the past 5 years, significant progress has been achieved in further understanding of drug resistance-related efflux transporters and this review focuses on the latest studies in this field since 2003. This has been demonstrated in multiple aspects that include but are not limited to: further molecular and biochemical characterization of the known drug efflux pumps and identification of novel drug efflux pumps; structural elucidation of the transport mechanisms of drug transporters; regulatory mechanisms of drug efflux pumps; determining the role of the drug efflux pumps in other functions such as stress responses, virulence and cell communication; and development of efflux pump inhibitors. Overall, the multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.read more
Citations
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Antibiotic resistance and its cost: is it possible to reverse resistance?
Dan I. Andersson,Diarmaid Hughes +1 more
TL;DR: The findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced, and that the rate of reversibility will be slow at the community level.
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The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria
TL;DR: This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps, with particular focus on AcrAB-TolC and Mex pumps.
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Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies
TL;DR: The mechanism of antibiotic resistance in P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections.
Journal ArticleDOI
Pseudomonas aeruginosa: resistance to the max.
TL;DR: The organism's propensity to grow in vivo as antimicrobial-tolerant biofilms and the occurrence of hypermutator strains that yield antimicrobial resistant mutants at higher frequency also compromise anti-pseudomonal chemotherapy.
Journal ArticleDOI
Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria
Hiroshi Nikaido,Jean-Marie Pagès +1 more
TL;DR: The recent investigation on the efflux pump AcrB at its structural and physiological levels, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may pave the way towards the rational development of an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms.
References
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Journal ArticleDOI
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Journal Article
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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.
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Persister cells, dormancy and infectious disease
TL;DR: The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.