Required criteria of drug efflux pump inhibitors to disrupt the function of AcrB subunit protein from AcrAB-TolC multidrug efflux pump from Escherichia coli

Abstract

The infections of multidrug-resistant bacteria, particularly the infections caused by Gram-negative bacterial infections, are considered the main global serious health problems. Multidrug-resistant bacteria possess different resistance mechanisms, the most important of which are drug efflux pumps due to their function in recognizing harmful compounds, especially antibiotics, and expelling, them outside the cell, which leads to a decrease in their concentration to sub-toxic levels and losing their effectiveness. One of the most important approaches that can be used to inhibit drug efflux pumps is using small molecule inhibitors targeting specifically pumps to prevent their expelling antibiotics from inside the cell before reaching the required concentration that kills bacteria. The drug efflux pumps inhibition approach is emerging as a new attractive and promising approach in reversing antibiotic resistance in many clinically relevant pathogenic bacteria. This review will discuss the requirements that must be met in inhibitors that target AcrB, which is the main subunit protein responsible for multiple antibiotic resistance in the main pump of AcrAB-TolC which belongs to E. coli, which were specifically chosen due to their various homologs in many Gram-negative bacteria which all of which are implicated in multi-drug resistance (MDR), and the availability of the pump's functions and chemical structures.

Keywords

• Required criteria of inhibitors
• Inhibitors of drug efflux pump
• Multidrug efflux pump
• Superfamily efflux pump RND
• E. coli
• AcrAB-TolC