Simplified model of antibiotic fluxes in bacterial cells without efflux pumps (A), cells expressing a single-component pump (B), cells expressing a multicomponent efflux pump (C), and cells simultaneously expressing a multicomponent and a single-component pump (D). The models show the fluxes of antibiotics at steady state. External concentrations of antibiotics are equal to MICs and the density of dots corresponds approximately to the concentration of antibiotic in each compartment. In each case, the concentration of antibiotics in the cytoplasm is the same and is sufficient to inhibit the target for antibiotics. Arrows indicate directions, and their thicknesses indicate rates of flux. The thick line separating the periplasm and the external medium indicates the low permeability of the outer membrane (OM) compared to the inner membrane (IM). In cells without efflux pumps (A), all compartments are essentially in equilibrium. In cells expressing a single-component pump (B), which extrudes substrates into the periplasm, thus balancing the rapid influx across the inner membrane, the external medium and the periplasm are in equilibrium, and the gradient of concentrations (R1) exists at the inner membrane. In cells expressing a multicomponent efflux pump (C), which extrudes antibiotics in the external medium, bypassing the outer membrane barrier, the cytoplasm and the periplasm are in equilibrium, and the gradient of concentrations (R2) emerges at the outer membrane. In the case of simultaneous expression of both efflux pumps (D), respective concentration gradients are maintained at both the inner and the outer membranes. This results in a multiplicative effect on drug resistance.