Components of the Gram-negative cellular envelope. (A) The cellular envelope of Gram-negative bacteria (right) contains two lipid membranes, while Gram-positive bacteria (left) have only one lipid membrane. The outer leaflet of the outer-membrane of Gram-negative bacteria is composed of lipopolysaccharides (LPS). Most small molecules are unable to passively diffuse at an appreciable rate through the LPS layer. Instead, molecules enter through channel proteins called porins (yellow). Almost all compounds, however, are subject to multidrug efflux pumps. (B) The structure of lipid A. The core oligosaccharide is linked to the 6′ carbon. (C) Top view of OmpF, the prototypical porin. A negatively-charged loop extends into the center of the cavity across from a positively-charged wall, creating a narrow constriction site and preventing the passage of many compounds. The crystal structure was generated from PDB 1opf using the Molecular Operating Environment software.