Outer membrane lipoprotein NlpI scaffolds peptidoglycan hydrolases within multi-enzyme complexes in Escherichia coli

Manuel Banzhaf, Hamish Cl Yau, Jolanda Verheul, Adam Lodge, George Kritikos, André Mateus, Baptiste Cordier, Ann Kristin Hov, Frank Stein, Morgane Wartel, Manuel Pazos, Alexandra S Solovyova, Eefjan Breukink, Sven van Teeffelen, Mikhail M Savitski, Tanneke den Blaauwen, Athanasios Typas, Waldemar Vollmer

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
168 Downloads (Pure)


The peptidoglycan (PG) sacculus provides bacteria with the mechanical strength to maintain cell shape and resist osmotic stress. Enlargement of the mesh-like sacculus requires the combined activity of peptidoglycan synthases and hydrolases. In Escherichia coli, the activity of two PG synthases is driven by lipoproteins anchored in the outer membrane (OM). However, the regulation of PG hydrolases is less well understood, with only regulators for PG amidases having been described. Here, we identify the OM lipoprotein NlpI as a general adaptor protein for PG hydrolases. NlpI binds to different classes of hydrolases and can specifically form complexes with various PG endopeptidases. In addition, NlpI seems to contribute both to PG elongation and division biosynthetic complexes based on its localization and genetic interactions. Consistent with such a role, we reconstitute PG multi-enzyme complexes containing NlpI, the PG synthesis regulator LpoA, its cognate bifunctional synthase, PBP1A, and different endopeptidases. Our results indicate that peptidoglycan regulators and adaptors are part of PG biosynthetic multi-enzyme complexes, regulating and potentially coordinating the spatiotemporal action of PG synthases and hydrolases.

Original languageEnglish
Article numbere102246
Number of pages20
JournalThe EMBO journal
Issue number5
Early online date3 Feb 2020
Publication statusPublished - 2 Mar 2020

Bibliographical note

© 2020 The Authors. Published under the terms of the CC BY 4.0 license.


  • bacterial cell envelope
  • endopeptidase
  • outer membrane lipoprotein
  • penicillin-binding protein
  • peptidoglycan

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology


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