EFFLUX PUMPS AS A PHARMACOLOGICAL TARGET TO COMBAT ANTIBIOTIC RESISTANCE

Abstract

Backround. Antibiotic resistance is the resistance of bacteria to antimicrobial drugs to which they were previously sensitive. A particular danger is the spread of multidrug-resistant healthcare-associated infections of "ESKAPE" group. Among the mechanisms of antibiotic resistance of these bacteria, the activation of efflux pumps attracts special attention.
 Aim: to review the current data on the possibility of using efflux pumps as targets for pharmacological action to overcome antibiotic resistance.
 Materials and methods. Analysis of the data presented in PubMed by keywords "antimicrobial resistance", "efflux pumps", "efflux pump inhibitors".
 Results. Multidrug efflux pumps are transmembrane transporter proteins that are located in the bacterial cell membrane and periplasm, they are naturally expressed, removing most of the clinically relevant antibiotic from the internal environment of the cell to the external environment, reducing its intracellular concentration. It is promising to combine certain antibiotics with efflux pump inhibitors, this allows to reduce the therapeutic dose of antibiotics and prevent the formation of bacterial biofilms. Data on the study of the effectiveness of well-known drugs sertraline, trimethoprim, thioridazine, diclofenac sodium, ibuprofen, nitroglycerin, metformin, and verapamil as efflux pump inhibitors are presented. The use of compounds obtained from plants (for example, berberine, artesunate and curcumin inhibit the activity of the efflux pump of gram-negative bacilli E. coli and P. aeruginosa), vegetables (in particular, Momordica balsamina), seeds of thistle, pepper, cumin, essential oils, etc. is promising.
 Conclusion. Thus, inhibition of efflux pumps may be a potential way to improve antibiotic activity. The advantage of efflux pumps inhibitors is the difficulty of developing resistance against them in bacteria. It is advisable to conduct in vivo studies to confirm their activity and clinical effectiveness.