Research Article

Dual Molecular Signals Mediate the Bacterial Response to Outer-Membrane Stress

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Science  17 May 2013:
Vol. 340, Issue 6134, pp. 837-841
DOI: 10.1126/science.1235358

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Stress Inside Out

In Gram-negative bacteria, the integrity of the outer membrane is crucial for survival and is an important aspect of resistance to antibiotics. The biogenesis of the major components lipopolysaccharide (LPS) and outer-membrane protein (OMP) of the outer membrane begins in the cytoplasmic compartment, involves export across the inner membrane and transport through the periplasm, and finally requires active insertion into the outer membrane by specialized assembly machines. Lima et al. (p. 837) supply results for a model in which serious defects in LPS biogenesis also create problems for OMP biogenesis, thereby producing the two signals needed to activate the σE stress response pathway.


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 the 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.

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