Efflux pump and its inhibitors: Cause and cure for multidrug resistance

Abstract

Multidrug resistance has become a threat to global public health as a result of resistance of microbes toward several drugs leading to prolonged period of illness, disability, incapacity, and death. Such multidrug resistance is seen principally in organisms involved in nosocomial infections also called as hospital-acquired infections. Enterococcus species, Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species (ESKAPE pathogens) are one of the major causes of nosocomial infections. Organisms acquire resistance to various antibiotics because of repetitive use and unprescribed medication. There are different mechanisms responsible for multidrug resistance, viz. inactivation by enzymes or alteration of drug, modification of drug binding site, reduction in intracellular drug accumulation, formation of biofilm, and preventing drug access to target (efflux pump). Among these the most common mechanism adopted by the organism is efflux pump and is profoundly seen in P. aeruginosa , Escherichia coli , and Candida albicans. An efflux pump is the channel that actively exports antimicrobials and other compounds out of the cell. Molecules involved in the inhibition of efflux mechanisms are known as efflux pump inhibitors. In this review, we mainly focus on the efflux pump as the major cause of escape of pathogens (mainly ESKAPE pathogens) from the action of antibiotics and strategies that can be used to overcome the resistance caused by these pumps.