Fig 2. Characteristic regimes of drug accumulation in bacteria.

(a). Steady state (ss) drug levels in the periplasm plotted against the equilibrium (eq) drug concentration (X_p), which would be observed in the absence of active fluxes. Note that X_p is proportional to the external drug concentration, X_p = k₁O/k₂. Solutions to Eq 2 are shown for cells without active drug efflux (V = 0), or with the indicated values of the barrier constant B. Asymptotic behavior of the plots (Eq 11) is shown with dashed lines together with the underlying equations. The variables are defined in Eq 2; α = (1-B)/(1+B). Note the existence of two regimes, of efficient (B>1) and inefficient (B<1) efflux. (b). The relationship between the steady state and equilibrium drug concentrations in the periplasm of cells with active drug efflux (K_E > 1) but no outer membrane barrier (B = 0). The transition between regimes of efficient and inefficient efflux occurs when the periplasmic drug concentration reaches the transporter’s Michaelis constant Km. (c). The initial rate of drug accumulation in the cytoplasm as a function of its external concentration. Dashed lines mark the asymptotes to the plots.