Regulated proteolysis of a cross-link-specific peptidoglycan hydrolase contributes to bacterial morphogenesis

Peptidoglycan (PG) is a unique and essential cross-linked, bag-like macromolecule that completely encases the cytoplasmic membrane and confers shape and rigidity to a bacterial cell. Therefore, bacterial cell growth is tightly coupled to PG expansion, requiring the coordinate activity of hydrolases that cleave the cross-links and synthases that catalyze the cross-link formation. This study highlights the importance of cross-link cleavage and its regulation in PG biogenesis by demonstrating the modulation of a cross-link-specific PG hydrolytic enzyme, MepS, by a previously unidentified degradation system consisting of an outer membrane lipoprotein, NlpI and a periplasmic protease, Prc. These studies facilitate better understanding of bacterial cell wall synthesis, which is a target of several antimicrobial therapeutic agents.