Fig 4. Contributions of active drug efflux and the outer membrane barrier to drug susceptibility of a bacterium.

(a) Effects of the inactivation of drug efflux are modeled for bacteria with efficient (B > 1) and inefficient (B < 1) efflux. Drug concentrations are measured in the units of Km, K_E equals 10 for all compounds. Depending on the intracellular inhibition constant of a compound, K_I, inactivation of efflux can reduce its observed inhibitory concentration 3-, 7- or 37-fold, respectively, in the case of inefficient (B < 1, K_I > Km), partially efficient (B < 1, K_I < Km) or efficient (B > 1, K_I < Km) efflux. (b). Growth inhibition of bacteria with defects in multidrug efflux or membrane permeability by Hoechst. The IC₅₀ values (in μM) are shown in parenthesis. (c). The ratio of IC₅₀s of azithromycin (AZI), ciprofloxacin (CIP) and Hoechst (HT) for TolC⁺ and ΔTolC cells measured in the absence (no Pore) or presence (+Pore) of overproduced FhuA* (±SD; n ≥ 2) plotted on a logarithmic scale.