Effectiveness of efflux pump inhibitors as biofilm disruptors and resistance breakers in gram- negative (ESKAPEE) bacteria

Akif Reza, J. Mark Sutton, Khondaker Miraz Rahman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

69 Citations (Scopus)


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.

Original languageEnglish
Article number229
Issue number4
Publication statusPublished - Dec 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • Antibiotic potentiation
  • Antimicrobial resistance
  • Biofilm
  • ESKAPEE pathogens
  • Efflux pump inhibitors
  • Gram-negative bacteria


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