Modulation of bacterial cell size and growth rate via activation of a cell envelope stress response

Cells mount elaborate responses to environmental stresses across multiple scales. In enterobacteria, the Rcs phosphorelay is activated by cell-envelope damage and by alterations to periplasmic thickness and cell width. To explore Rcs activation in the absence of external stresses, we investigated the physiological and morphological consequences of Rcs activation in Escherichia coli. We used an inducible variant of the lipoprotein RcsF that mislocalizes to the inner membrane (RcsFIM) and constitutively activates the Rcs system. RcsFIM expression slowed growth and reduced the cell length added per cell cycle, independent of the Rcs-controlled capsule production. Concurrently, concentration of the division protein FtsZ increased and division rings formed closer together in filamentous cells. Depletion of the Rcs negative regulator IgaA also slowed growth and elevated FtsZ levels, indicating that IgaA is essential due to growth inhibition in its absence. In contrast, treatment with the Rcs-activating antibiotic A22 did not affect growth rate or FtsZ concentration, and restored normal-growth in cells in which the Rcs system was pre-induced with RcsFIM expression. Hence the cellular response to A22 buffers the Rcs-dependent effect on cell growth. Together, our findings suggest that Rcs modulates cell division indirectly through growth-rate changes, and that activation of the same pathway in different contexts can produce distinct physiological outcomes.