Lipopolysaccharide Transport System Links Physiological Roles of σ and ArcA in the Cell Envelope Biogenesis in Shewanella oneidensis.

The bacterial cell envelope is not only a protective structure that surrounds the cytoplasm but also the place where a myriad of biological processes take place. This multilayered complex is particularly important for electroactive bacteria such as Shewanella oneidensis, as it generally hosts branched electron transport chains and numerous reductases for extracellular respiration. However, little is known about how the integrity of the cell envelope is established and maintained in these bacteria. By tracing the synthetic lethal effect of Arc two-component system and σ in S. oneidensis, in this study, we identified the lipopolysaccharide transport (Lpt) system as the determining factor. Both Arc and σ, by regulating transcription of and , respectively, are required for the Lpt system to function properly. The ArcA loss results in an LptFG shortage that triggers activation of σ and leads to LptD overproduction. LptFG and LptD at abnormal levels cause a defect in the lipopolysaccharide (LPS) transport, leading to cell death unless σ-dependent envelope stress response is in place. Overall, our report reveals for the first time that Arc works together with σ to maintain the integrity of the S. oneidensis cell envelope by participating in the regulation of the LPS transport system. Arc is a well-characterized global regulatory system that modulates cellular respiration by responding to changes in the redox status in bacterial cells. In addition to regulating expression of respiratory enzymes, Shewanella oneidensis Arc also plays a critical role in cell envelope integrity. The absence of Arc and master envelope stress response (ESR) regulator σ causes a synthetic lethal phenotype. Our research shows that the Arc loss downregulates expression, leading to cell envelope defects that require σ-mediated ESR for viability. The complex mechanisms revealed here underscore the importance of the interplay between global regulators in bacterial adaption to their natural inhabits.