Figure 4.

Principal mechanisms for inhibiting multidrug efflux pumps. An efflux pump is schematically represented as an orange rectangle crossing the bacterial membrane. A generic antimicrobial agent is represented as a grey dot. The flux of the pump substrate is depicted as an arrow. The red cross represents the inhibition of the substrate transfer along the pump or of a constituent of the transporter or the source of energy. (Top left) Intracellular accumulation of an antimicrobial drug with a conformation different (green square) from that for which the pump is able to expel; (top right) increased presence of the drug inside the cells due to the blockage of the efflux pump assembly; (middle) inhibition of the proton force mediating the efflux pump functions; (lower left) intracellular increase in the antimicrobial drug following the selective inhibition of some of the efflux pump components that can be in the outer membrane, the inner membrane, or the cytoplasmic side; (lower right) intracellular accumulation of the antimicrobial drug following the passage of a competitive inhibitor across the efflux pump channel.