Regulation of Peptidoglycan Synthesis by Outer-Membrane Proteins

TLDR

Growth of the mesh‑like peptidoglycan sacculus between the bacterial inner and outer membranes is tightly regulated to maintain cellular integrity, shape, and division, yet the precise spatiotemporal control by cytoskeletal elements remains poorly understood. We demonstrate that outer‑membrane lipoproteins LpoA and LpoB bind their cognate PG synthases PBP1A and PBP1B, stimulate transpeptidase activity to facilitate sacculus attachment, with LpoB localizing to septa and contributing to outer‑membrane constriction, and that these regulatory interactions are specific to γ‑proteobacteria.

Abstract

Growth of the mesh-like peptidoglycan (PG) sacculus located between the bacterial inner and outer membranes (OM) is tightly regulated to ensure cellular integrity, maintain cell shape, and orchestrate division. Cytoskeletal elements direct placement and activity of PG synthases from inside the cell, but precise spatiotemporal control over this process is poorly understood. We demonstrate that PG synthases are also controlled from outside of the sacculus. Two OM lipoproteins, LpoA and LpoB, are essential for the function, respectively, of PBP1A and PBP1B, the major E. coli bifunctional PG synthases. Each Lpo protein binds specifically to its cognate PBP and stimulates its transpeptidase activity, thereby facilitating attachment of new PG to the sacculus. LpoB shows partial septal localization, and our data suggest that the LpoB-PBP1B complex contributes to OM constriction during cell division. LpoA/LpoB and their PBP-docking regions are restricted to γ-proteobacteria, providing models for niche-specific regulation of sacculus growth.