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Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli), in particular, have proven t...

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Detalles Bibliográficos
Autores principales: Reza, Akif, Sutton, J. Mark, Rahman, Khondaker Miraz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963839/
https://www.ncbi.nlm.nih.gov/pubmed/31752382
http://dx.doi.org/10.3390/antibiotics8040229
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author Reza, Akif
Sutton, J. Mark
Rahman, Khondaker Miraz
author_facet Reza, Akif
Sutton, J. Mark
Rahman, Khondaker Miraz
author_sort Reza, Akif
collection PubMed
description Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli), in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.
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spelling pubmed-69638392020-01-27 Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria Reza, Akif Sutton, J. Mark Rahman, Khondaker Miraz Antibiotics (Basel) Review Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli), in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens. MDPI 2019-11-19 /pmc/articles/PMC6963839/ /pubmed/31752382 http://dx.doi.org/10.3390/antibiotics8040229 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Reza, Akif
Sutton, J. Mark
Rahman, Khondaker Miraz
Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title_full Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title_fullStr Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title_full_unstemmed Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title_short Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria
title_sort effectiveness of efflux pump inhibitors as biofilm disruptors and resistance breakers in gram-negative (eskapee) bacteria
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963839/
https://www.ncbi.nlm.nih.gov/pubmed/31752382
http://dx.doi.org/10.3390/antibiotics8040229
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