Efflux of Cytoplasmically Acting Antibiotics from Gram-Negative Bacteria: Periplasmic Substrate Capture by Multicomponent Efflux Pumps Inferred from Their Cooperative Action with Single-Component Transporters

In gram-negative bacteria, coexpression of single- and multicomponent efflux pumps may result in multiplicative enhancement of the level of resistance against cytoplasmically acting antibiotics. Here, a simple model is presented to show that this cooperative effect can be accounted for only if substrate capture by the multicomponent efflux transporter occurs in the periplasm but not the cytosol.