title: The cell wall precursor lipid II acts as a molecular signal for the Ser/Thr kinase PknB of Staphylococcus aureus.
abstract: The assembly of the bacterial cell wall requires synchronization of a multitude of biosynthetic machineries and regulatory networks. The eukaryotic-like serine/threonine kinase PknB has been implicated in coordinating cross-wall formation, autolysis and cell division in Staphylococcus aureus. However, the signal molecule sensed by this kinase remained elusive so far. Here, we provide compelling biochemical evidence that PknB interacts with the ultimate cell wall precursor lipid II, triggering kinase activity. Moreover, we observed crosstalk of PknB with the two component system WalKR and identified the early cell division protein FtsZ as another PknB phosphorylation substrate in S. aureus. In agreement with the implied role in regulation of cell envelope metabolism, we found PknB to preferentially localize to the septum of S. aureus and the PASTA domains to be crucial for recruitment to this site. The data provide a model for the contribution of PknB to control cell wall metabolism and cell division.
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hardt
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Engels
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Rausch
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Gajdiss
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Ulm
authors.affiliation: Interfaculty Institute for Microbiology and Infection Medicine, Department for Microbial Bioactive Compounds, University of Tuebingen, Tuebingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Sass
authors.affiliation: Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Ohlsen
authors.affiliation: German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany; Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany. Electronic address: tanja@microbiology-bonn.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany. Electronic address: grein@uni-bonn.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Grein
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000378:metabolism*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C119939:YycF protein, Bacteria; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D017346:Protein Serine-Threonine Kinases
keywords: Cell division; Lipid II; Phosphorylation; Serine/threonine protein kinase; Staphylococcus aureus