ActS activates peptidoglycan amidases during outer membrane stress in Escherichia coli

• DOI: 10.1111/mmi.14712
• Publication Date: 2021-03-04T13:00:31Z
• Authors: Carlos K. Gurnani...; Matthias Winkle; Alessandra M. Mar...; Jacob Biboy; Niccolo Morè; Patrick Moynihan; Manuel Banzhaf; Waldemar Vollmer; Alessandra Polissi
• Keywords: Lipopolysaccharides; 0301 basic medicine; 0303 health sciences; Escherichia coli Proteins; Cell Membrane; Carboxypeptidases; N-Acetylmuramoyl-L-alanine Amidase; Peptidoglycan; Serine-Type D-Ala-D-Ala Carboxypeptidase; 03 medical and health sciences; Bacterial Outer Membrane; Cell Wall; Stress, Physiological; Endopeptidases; Escherichia coli; Penicillin-Binding Proteins; Peptidoglycan Glycosyltransferase; Research Articles; Gene Deletion; cell division; cell envelope; Escherichia coli; lipopolysaccharide; peptidoglycan;; Escherichia coli; cell division; cell envelope; lipopolysaccharide; peptidoglycan; Plasmids

AbstractThe integrity of the cell envelope of E. coli relies on the concerted activity of multi‐protein machineries that synthesize the peptidoglycan (PG) and the outer membrane (OM). Our previous work found that the depletion of lipopolysaccharide (LPS) export to the OM induces an essential PG remodeling process involving LD‐transpeptidases (LDTs), the glycosyltransferase function of PBP1B and the carboxypeptidase PBP6a. Consequently, cells with defective OM biogenesis lyse if they lack any of these PG enzymes. Here we report that the morphological defects, and lysis associated with a ldtF mutant with impaired LPS transport, are alleviated by the loss of the predicted OM‐anchored lipoprotein ActS (formerly YgeR). We show that ActS is an inactive member of LytM‐type peptidoglycan endopeptidases due to a degenerated catalytic domain. ActS is capable of activating all three main periplasmic peptidoglycan amidases, AmiA, AmiB, and AmiC, which were previously reported to be activated only by EnvC and/or NlpD. Our data also suggest that in vivo ActS preferentially activates AmiC and that its function is linked to cell envelope stress.