title: SEDS proteins are a widespread family of bacterial cell wall polymerases.
abstract: Elongation of rod-shaped bacteria is mediated by a dynamic peptidoglycan-synthetizing machinery called the Rod complex. Here we report that, in Bacillus subtilis, this complex is functional in the absence of all known peptidoglycan polymerases. Cells lacking these enzymes survive by inducing an envelope stress response that increases the expression of RodA, a widely conserved core component of the Rod complex. RodA is a member of the SEDS (shape, elongation, division and sporulation) family of proteins, which have essential but ill-defined roles in cell wall biogenesis during growth, division and sporulation. Our genetic and biochemical analyses indicate that SEDS proteins constitute a family of peptidoglycan polymerases. Thus, B. subtilis and probably most bacteria use two distinct classes of polymerase to synthesize their exoskeleton. Our findings indicate that SEDS family proteins are core cell wall synthases of the cell elongation and division machinery, and represent attractive targets for antibiotic development.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Meeske
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Eammon P
authors.initials: EP
authors.lastname: Riley
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Robins
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mekalanos
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave, Boston, Massachusetts 02115, USA.|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahne
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave, Boston, Massachusetts 02115, USA.|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Kruse
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Bernhardt
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Rudner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D009154:Mutation; D009844:Oligosaccharides / Q000494:pharmacology; D046915:Penicillin-Binding Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis*; D046928:Peptidoglycan Glycosyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D058105:Polymerization
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009844:Oligosaccharides; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D046928:Peptidoglycan Glycosyltransferase; C419802:moenomycin