How hydrophobic molecules traverse the outer membranes of Gram-negative bacteria

Abstract

The outer membrane (OM) of Gram-negative bacteria provides an effective barrier to their often-harsh extracellular milieu. In particular, the outer leaflet of the OM is not a canonical monolayer of phospholipids. Rather, it is composed of lipopolysaccharide (LPS), a molecule generally consisting of a core of Lipid A decorated with inner and outer core oligosaccharides. The oligosaccharides extend ∼30 A above the plane of the lipid headgroups of the outer leaflet. As such, it is an effective permeability barrier against potentially harmful compounds (1). However, obviously, permeability is required for bacterial survival; no bacterium is an island, as it were. For example, uptake of nutrients is essential, and OM transport proteins are required to conduct this function. The recent paper of Lepore et al. (2) has significantly extended our understanding of how hydrophobic molecules are transported across the OM. With rare exception (e.g., ref. 3), virtually all OM proteins are β-barrels, consisting of an even number of eight to twenty-four of β-strands forming a pore-like structure. Many of these OM pore-like β-barrels are classified as porins, and most nutrient uptake is accomplished by them. The effective aperture of the porin is dictated by the number of β-strands, and the aperture size then dictates the size (and shape) of the solutes that can diffuse through them. Porins function passively, permitting the energy-independent diffusion of solute molecules with a molecular mass of 600 Da or less downhill across a concentration gradient, through the porin's β-barrel, and into the periplasm. Another class of energy-independent OM transporters uses low-affinity binding sites that effectively serve to amplify small concentration gradients at the site of the transporter (4).