The Lpp detaching enzyme DpaA post-translationally controls the level of PG amidase activator ActS to enable survival under severe OM biogenesis defect in Escherichia coli

The coordinated growth of the three-layered cell envelope of Gram-negative bacteria is critical under stress conditions or when the assembly of one of the layers is compromised. In Escherichia coli, when the export of lipopolysaccharide (LPS) to the outer membrane (OM) is defective, the DpaA protein is required to avoid cell lysis. DpaA is an enzyme that detaches the lipoprotein Lpp from peptidoglycan (PG), a non-essential function under normal growth conditions. The lysis of LPS export stressed cells lacking DpaA does not happen in the absence of ActS, a LytM protein that contributes to the activation of PG amidases, which hydrolyze septal PG to enable separation of daughter cells. As ActS is dispensable under non-stress conditions it is believed that in OM stressed cells lacking DpaA, spurious activation of amidases through ActS contribute to cell lysis. However, how the functional interaction between DpaA and ActS prevents cell lysis under envelope stress is not understood. Our recent data suggest that the Lpp detachment activity of DpaA is not required to allow cell survival under stress and that spurious activation of amidases does not depend on increased expression of actS under stress conditions. Instead, we found that under stress conditions and in a DpaA dependent way, the cell keeps the level of ActS low implicating a novel post-translational mechanism to control the relative abundance of ActS in the cell.