Bacterial cleanup: lateral diffusion of hydrophobic molecules through protein channel walls

Abstract

The outer membrane (OM) of Gram-negative bacteria forms a very efficient barrier against the permeation of both hydrophilic and hydrophobic compounds, owing to the presence of lipopolysaccharides on the outside of the cell. Although much is known about the OM passage of hydrophilic molecules, it is much less clear how hydrophobic molecules cross this barrier. Members of the FadL channel family, which are widespread in Gram-negative bacteria, are so far the only proteins with an established role in the uptake of hydrophobic molecules across the OM. Recent structural and biochemical research has shown that these channels operate according to a unique lateral diffusion mechanism, in which the substrate moves from the lumen of the barrel into the OM via an unusual opening in the wall of the barrel. Understanding how hydrophobic molecules cross the OM is not only of fundamental importance but could also have applications in the design of novel, hydrophobic drugs, biofuel production and the generation of more efficient bacterial biodegrader strains.