The LpoA activator is required to stimulate the peptidoglycan polymerase activity of its cognate cell wall synthase PBP1a
Marios Frantzeskos Sardis, Jessica L. Bohrhunter, Neil G. Greene, Thomas G. Bernhardt
Abstract
Significance Class A penicillin-binding proteins (aPBPs) assemble the bacterial cell wall and are the targets of penicillin and related β-lactam antibiotics. In gram-negative bacteria, the aPBPs require outer membrane lipoproteins to function. However, little is known about how these proteins promote the activity of their cognate synthases in cells. Here, we show that one of these lipoproteins, called LpoA, has a much more pronounced effect on aPBP activity in cells than anticipated from biochemical studies. It not only modulates the cross-linking of cell wall polymers but is also required for the aPBP to make the polymers in the first place. Our findings therefore provide insights into the regulation of an important class of antibiotic targets in their native cellular context.