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Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria
Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854755/ https://www.ncbi.nlm.nih.gov/pubmed/36671381 http://dx.doi.org/10.3390/antibiotics12010180 |
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author | Compagne, Nina Vieira Da Cruz, Anais Müller, Reinke T. Hartkoorn, Ruben C. Flipo, Marion Pos, Klaas M. |
author_facet | Compagne, Nina Vieira Da Cruz, Anais Müller, Reinke T. Hartkoorn, Ruben C. Flipo, Marion Pos, Klaas M. |
author_sort | Compagne, Nina |
collection | PubMed |
description | Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics. AMR is caused by several mechanisms, among which the (over)expression of multidrug efflux pumps plays a central role. Multidrug efflux pumps are transmembrane transporters, naturally expressed by Gram-negative bacteria, able to extrude and confer resistance to several classes of antibiotics. Targeting them would be an effective way to revive various options for treatment. Many efflux pump inhibitors (EPIs) have been described in the literature; however, none of them have entered clinical trials to date. This review presents eight families of EPIs active against Escherichia coli or Pseudomonas aeruginosa. Structure–activity relationships, chemical synthesis, in vitro and in vivo activities, and pharmacological properties are reported. Their binding sites and their mechanisms of action are also analyzed comparatively. |
format | Online Article Text |
id | pubmed-9854755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98547552023-01-21 Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria Compagne, Nina Vieira Da Cruz, Anais Müller, Reinke T. Hartkoorn, Ruben C. Flipo, Marion Pos, Klaas M. Antibiotics (Basel) Review Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics. AMR is caused by several mechanisms, among which the (over)expression of multidrug efflux pumps plays a central role. Multidrug efflux pumps are transmembrane transporters, naturally expressed by Gram-negative bacteria, able to extrude and confer resistance to several classes of antibiotics. Targeting them would be an effective way to revive various options for treatment. Many efflux pump inhibitors (EPIs) have been described in the literature; however, none of them have entered clinical trials to date. This review presents eight families of EPIs active against Escherichia coli or Pseudomonas aeruginosa. Structure–activity relationships, chemical synthesis, in vitro and in vivo activities, and pharmacological properties are reported. Their binding sites and their mechanisms of action are also analyzed comparatively. MDPI 2023-01-15 /pmc/articles/PMC9854755/ /pubmed/36671381 http://dx.doi.org/10.3390/antibiotics12010180 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Compagne, Nina Vieira Da Cruz, Anais Müller, Reinke T. Hartkoorn, Ruben C. Flipo, Marion Pos, Klaas M. Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title | Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title_full | Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title_fullStr | Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title_full_unstemmed | Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title_short | Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria |
title_sort | update on the discovery of efflux pump inhibitors against critical priority gram-negative bacteria |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854755/ https://www.ncbi.nlm.nih.gov/pubmed/36671381 http://dx.doi.org/10.3390/antibiotics12010180 |
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