Science 340, 837–841 (2013)

Credit: ROBERT SAUER

In Gram-negative bacteria, σE enhances transcription of genes whose products protect or restore the outer membrane after stress-induced damage. Periplasmic accumulation of outer-membrane proteins (OMPs) in E. coli activates degradation of RseA, a transmembrane protein and σE inhibitor, by the DegS protease. Inhibition of the RseA-binding partner RseB is also required to allow degradation and σE function, but the nature of the inhibiting signal is unknown. Lima et al. now show that lipopolysaccharide (LPS) and its variants can dissociate RseA–RseB complexes in vitro. Portions of LPS, including Lipid A fragments that contain GlcNAc sugars and N-linked acyl chains, also dissociate RseA–RseB. LPS fragments bind RseB directly and stabilize a tetrameric form that does not bind RseA. Using a partially functional LptD translocon, which inserts LPS into the outer membrane, the authors show that increased periplasmic LPS relieves RseB inhibition of RseA cleavage and activates the stress response. These results suggest that periplasmic buildup of the two major outer membrane components allows bacteria to sense and respond to stress: LPS frees the RseA inhibitor of σE to allow its degradation, and OMPs activate this degradation reaction.