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

1
Institute of Pharmaceutical Science, King’s College London, London, SE1 9NH, UK
2
National Infections Service, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK
*
Author to whom correspondence should be addressed.
Antibiotics 2019, 8(4), 229; https://doi.org/10.3390/antibiotics8040229
Received: 21 October 2019 / Revised: 7 November 2019 / Accepted: 12 November 2019 / Published: 19 November 2019
(This article belongs to the Section Novel Antimicrobial Agents)
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. View Full-Text
Keywords: antimicrobial resistance; biofilm; efflux pump inhibitors; antibiotic potentiation; ESKAPEE pathogens; Gram-negative bacteria antimicrobial resistance; biofilm; efflux pump inhibitors; antibiotic potentiation; ESKAPEE pathogens; Gram-negative bacteria
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Reza, A.; Sutton, J.M.; Rahman, K.M. Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria. Antibiotics 2019, 8, 229.

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