title: SagB Glucosaminidase Is a Determinant of Staphylococcus aureus Glycan Chain Length, Antibiotic Susceptibility, and Protein Secretion.
abstract: The envelope of Staphylococcus aureus is comprised of peptidoglycan and its attached secondary polymers, teichoic acid, capsular polysaccharide, and protein. Peptidoglycan synthesis involves polymerization of lipid II precursors into glycan strands that are cross-linked at wall peptides. It is not clear whether peptidoglycan structure is principally determined during polymerization or whether processive enzymes affect cell wall structure and function, for example, by generating conduits for protein secretion. We show here that S. aureus lacking SagB, a membrane-associated N-acetylglucosaminidase, displays growth and cell-morphological defects caused by the exaggerated length of peptidoglycan strands. SagB cleaves polymerized glycan strands to their physiological length and modulates antibiotic resistance in methicillin-resistant S. aureus (MRSA). Deletion of sagB perturbs protein trafficking into and across the envelope, conferring defects in cell wall anchoring and secretion, as well as aberrant excretion of cytoplasmic proteins.
  
  
  OBJECTIVE
  Staphylococcus aureus is thought to secrete proteins across the plasma membrane via the Sec pathway; however, protein transport across the cell wall envelope has heretofore not been studied. We report that S. aureus sagB mutants generate elongated peptidoglycan strands and display defects in protein secretion as well as aberrant excretion of cytoplasmic proteins. These results suggest that the thick peptidoglycan layer of staphylococci presents a barrier for protein secretion and that SagB appears to extend the Sec pathway across the cell wall envelope.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Yvonne G Y
authors.initials: YG
authors.lastname: Chan
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Frankel
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, USA Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, Illinois, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, USA Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, Illinois, USA oschnee@bsd.uchicago.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011134:Polysaccharides; D006596:Hexosaminidases
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