Efflux pump inhibitors: new updates
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REVIEW
Efflux pump inhibitors: new updates Manaf AlMatar1 · Osman Albarri2 · Essam A. Makky1 · Fatih Köksal3 Received: 22 June 2020 / Revised: 4 September 2020 / Accepted: 7 September 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
Abstract The discovery of antibiotics ought to have ended the issue of bacterial infections, but this was not the case as it has led to the evolution of various mechanisms of bacterial resistance against various antibiotics. The efflux pump remains one of the mechanisms through which organisms develop resistance against antibiotics; this is because organisms can extrude most of the clinically relevant antibiotics from the interior cell environment to the exterior environment via the efflux pumps. Efflux pumps are thought to contribute significantly to biofilm formation as highlighted by various studies. Therefore, the inhibition of these efflux pumps can be a potential way of improving the activity of antibiotics, particularly now that the discovery of novel antibiotics is becoming tedious. Efflux pump inhibitors (EPIs) are molecules that can inhibit efflux pumps; they have been considered potential therapeutic agents for rejuvenating the activity of antibiotics that have already lost their activity against bacteria. However, studies are yet to determine the specific substrates for such pumps; the effect of altered efflux activity of these pumps on biofilm formation is still being investigated. A clear knowledge of the involvement of efflux pumps in biofilm development could aid in developing new agents that can interfere with their function and help to prevent biofilms formation; thereby, improving the outcome of treatment strategies. This review focuses on the novel update of EPIs and discusses the evidence of the roles of efflux pumps in biofilm formation; the potential approaches towards overcoming the increasing problem of biofilm-based infections are also discussed. Graphic abstract
Keywords Efflux pump inhibitors · Antimicrobial resistance · Biofilm · Bacterial infection
* Manaf AlMatar [email protected]; [email protected] * Essam A. Makky [email protected]; [email protected] Extended author information available on the last page of the article
Abbreviations EPIs Efflux pump inhibitors AMR Antimicrobial resistance HGT Horizontal gene transfer MDR Multidrug resistant EPs Efflux pumps ABC ATP-binding cassette
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CCCP Carbonyl cyanide m-chlorophenylhydrazine OMF Outer membrane factor NOV Novobiocin ERY Erythromycin aPDI Antimicrobial photodynamic inactivation PS Photosensitive dyes MB Methylene blue EPI-MB Efflux pump inhibitor-methylene blue TBO Toluidine blue O PABN Phenylalanine-arginine β-naphthylamide SMR Small multidrug resistance MATE Multidrug and toxin extrusion MFS Major facilitator superfamily RND Resistance-nodulation division PMF Proton motive force DARPin Designed ankyrin repeat proteins WT Wild type OM Outer membrane MPC The minimal potentiating concentration Et-Br Ethidium bromi
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