Dual molecular signals mediate the bacterial response to outer-membrane stress

In Gram-negative bacteria, outer-membrane integrity is essential for survival and is monitored by the σE stress-response system, which initiates damage-repair pathways. One activating signal is unassembled outer-membrane proteins. Using biochemical and genetic experiments in Escherichia coli, we found that off-pathway intermediates in lipopolysaccharide transport and assembly provided an additional required signal. These distinct signals, arising from disruptions in the transport and assembly of the major outer-membrane components, jointly determined the rate of proteolytic destruction of a negative regulator of the σE transcription factor, thereby modulating expression of stress-response genes. This dual-signal system permits a rapid response to dysfunction in outer-membrane biogenesis, while buffering responses to transient fluctuations in individual components, and may represent a broad strategy for bacteria to monitor their interface with the environment. The outer membrane (OM) is essential for survival of Gram-negative bacteria. In Escherichia coli, the σE stress-response system recognizes signals indicative of OM dysfunction and triggers an adaptive response by activating expression of gene product