Adaptation of bacterial proteome reveals a key role of the cell envelope in starvation survival

Bacteria reorganize their physiology and proteome upon entry to stationary phase. What part of this reorganization improves starvation survival is a difficult question, because the change in physiology includes a global reorganization of the proteome, envelope and metabolism of the cell. In this work, we aim to disentangle causation from correlation and identify changes in proteome resource allocation and physiology that directly contribute starvation survival. We found that a fundamental trade-off between fast growth and long survival is set by proteome allocation across diverse growth conditions and utilize this trade-off to statistically score over 2000 E. coli proteins for their global correlation with lifespan. The combined ranking allowed us to narrow down the set proteins that positively correlate with survival and validate the causal role of these proteins in improving starvation survival. Remarkably, we found that a significant fraction of survival genes is related in the cell envelope, i.e., periplasm and outer membrane. Indeed, we confirmed that the envelope integrity of E. coli plays a crucial role during starvation and verified that improving the mechanical stability of the outer membrane leads to better survival. Our results uncover a new protective feature of the outer membrane that adds to the growing evidence that the outer membrane is not only a barrier that prevents abiotic substances from reaching the cytoplasm, but essential for bacterial proliferation and survival. ### Competing Interest Statement The authors have declared no competing interest.