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

• Published in: Antibiotics (Basel) Vol. 8; no. 4; p. 229
• Main Authors: Reza, Akif, Sutton, J Mark, Rahman, Khondaker Miraz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.11.2019; MDPI
• Subjects: antibiotic potentiation; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Bacteria; Bacterial infections; Binding sites; biofilm; Biofilms; Chemical inhibitors; Control; Drug resistance; E coli; Efflux; efflux pump inhibitors; Environmental impact; Escherichia coli; eskapee pathogens; Evaluation; Extrusion; Gram-negative bacteria; Inhibitors; Klebsiella; Microbial drug resistance; Microbial mats; Nosocomial infections; Novels; Pathogenic microorganisms; Pathogens; Penicillin; Pharmaceutical industry; Pneumonia; Pseudomonas aeruginosa; Public health; Pumps; R&D; Research & development; Resistance factors; Review; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Tetracyclines; Thioridazine; United Kingdom; antibiotic potentiation; ESKAPEE pathogens; Antimicrobial resistance; Gram-negative bacteria; efflux pump inhibitors; biofilm
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics8040229

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens ( and ), 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.