Abstract
The worldwide dissemination of ‹multi-drug resistant› (MDR) pathogens has severely reduced the efficacy of our antibiotic arsenal and increased the frequency of therapeutic failure. MDR bacteria over-express efflux pumps and this active mechanism can extrude all classes of antibiotics from the cell.
It is necessary to clearly decipher the genetic, structural and functional aspects of this transport system in order to combat this polyselective mechanism. By understanding how efflux pumps work we may be able to develop a new group of antibacterial agents, collectively termed efflux reversals, including membrane permeabilisers, efflux pump inhibitors and flux-competitive agents, specific blockers, energy poisons, etc. Several chemical families of efflux pump inhibitors have been described and characterized. Among them several inhibitor compounds demonstrate efficient blocking of the efflux pump activity involved in the MDR phenotype as observed in many Gram-negative clinical isolates. This new family of molecules represents the first antibacterial class of compound specifically targeting active transport in the bacterial cell.
Keywords: Antibiotic, antibacterial agent, bacterial transporter, chemosensitizer, efflux pump, efflux pump inhibitor, drug transporter, Gram negative, bacteria, genetic regulation cascade, membrane permeability
Current Medicinal Chemistry
Title: An Original Deal for New Molecule: Reversal of Efflux Pump Activity, A Rational Strategy to Combat Gram-Negative Resistant Bacteria
Volume: 18 Issue: 19
Author(s): J.-M. Pages, L. Amaral and S. Fanning
Affiliation:
Keywords: Antibiotic, antibacterial agent, bacterial transporter, chemosensitizer, efflux pump, efflux pump inhibitor, drug transporter, Gram negative, bacteria, genetic regulation cascade, membrane permeability
Abstract: The worldwide dissemination of ‹multi-drug resistant› (MDR) pathogens has severely reduced the efficacy of our antibiotic arsenal and increased the frequency of therapeutic failure. MDR bacteria over-express efflux pumps and this active mechanism can extrude all classes of antibiotics from the cell.
It is necessary to clearly decipher the genetic, structural and functional aspects of this transport system in order to combat this polyselective mechanism. By understanding how efflux pumps work we may be able to develop a new group of antibacterial agents, collectively termed efflux reversals, including membrane permeabilisers, efflux pump inhibitors and flux-competitive agents, specific blockers, energy poisons, etc. Several chemical families of efflux pump inhibitors have been described and characterized. Among them several inhibitor compounds demonstrate efficient blocking of the efflux pump activity involved in the MDR phenotype as observed in many Gram-negative clinical isolates. This new family of molecules represents the first antibacterial class of compound specifically targeting active transport in the bacterial cell.
Export Options
About this article
Cite this article as:
Pages J.-M., Amaral L. and Fanning S., An Original Deal for New Molecule: Reversal of Efflux Pump Activity, A Rational Strategy to Combat Gram-Negative Resistant Bacteria, Current Medicinal Chemistry 2011; 18 (19) . https://dx.doi.org/10.2174/092986711796150469
DOI https://dx.doi.org/10.2174/092986711796150469 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Chemistry of Mycophenolic Acid - Synthesis and Modifications Towards Desired Biological Activity
Current Medicinal Chemistry Inhibitors of Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Burnout Syndrome in Emergency Physicians in Venezuela Early in the COVID-19 Pandemic
Current Psychiatry Research and Reviews Role of Oxidative Stress and Inflammation in Insomnia Sleep Disorder and Cardiovascular Diseases: Herbal Antioxidants and Anti-inflammatory Coupled with Insomnia Detection using Machine Learning
Current Pharmaceutical Design Quantitative Structure-Activity Studies on a Series of Migrastatin Analogs as Inhibitors of Cancer Cell Metastasis
Medicinal Chemistry QSAR Models for Proteins of Parasitic Organisms, Plants and Human Guests: Theory, Applications, Legal Protection, Taxes, and Regulatory Issues
Current Proteomics Quinic and Digallic acids from <i>Pistacia atlantica</i> Desf. Leaves Extracts as Potent Dual Effect Inhibitors against main Protease and RNA-dependent RNA Polymerase of SARS-CoV-2
Current Computer-Aided Drug Design Indoles and Related Compounds as Cannabinoid Ligands
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Activities of Substituted Benzoxazepine: A Review
Mini-Reviews in Organic Chemistry Emerging Targets in Neurodegeneration: New Opportunities for Alzheimer's Disease Treatment?
Current Topics in Medicinal Chemistry Qigefang Inhibits Migration, Invasion, and Metastasis of ESCC by Inhibiting Gas6/Axl Signaling Pathway
Recent Patents on Anti-Cancer Drug Discovery COVID-19 Anxiety and Washing Obsessive-compulsive Symptoms: Stress Coping Styles as a Mediator
Current Psychiatry Research and Reviews Synthesis and Biological Evaluation of Aromatase Inhibitors
Letters in Drug Design & Discovery Synthesis and Biological Evaluation of 2-amino-3-(3, 4, 5-trimethoxyphenylsulfonyl)-5-aryl thiophenes as a New Class of Antitubulin Agents
Medicinal Chemistry Machine Intelligence Techniques for the Identification and Diagnosis of COVID-19
Current Medicinal Chemistry Synthesis, Biological Evaluation, in Silico Docking and Virtual ADME Studies of Novel Isatin Analogs as Promising Antimicrobial Agents
Anti-Infective Agents The PIK3CA Gene as a Mutated Target for Cancer Therapy
Current Cancer Drug Targets Inhibition of RNA Virus Infections with Peptide-Conjugated Morpholino Oligomers
Current Pharmaceutical Design The Role of Celecoxib as a Potential Inhibitor in the Treatment of Inflammatory Diseases - A Review
Current Medicinal Chemistry Partial A1 Adenosine Receptor Agonists from a Molecular Perspective and Their Potential Use as Chronic Ventricular Rate Control Agents During Atrial Fibrillation (AF)
Current Topics in Medicinal Chemistry