title: RodA as the missing glycosyltransferase in Bacillus subtilis and antibiotic discovery for the peptidoglycan polymerase pathway.
abstract: The bacterial cell wall is a highly conserved essential component of most bacterial groups. It is the target for our most frequently used antibiotics and provides important small molecules that trigger powerful innate immune responses. The wall is composed of glycan strands crosslinked by short peptides. For many years, the penicillin-binding proteins were thought to be the key enzymes required for wall synthesis. RodA and possibly other proteins in the wider SEDS (shape, elongation, division and sporulation) family have now emerged as a previously unknown class of essential glycosyltranferase enzymes, which play key morphogenetic roles in bacterial cell wall synthesis. We provide evidence in support of this role and the discovery of small natural product molecules that probably target these enzymes. The SEDS proteins have exceptional potential as targets for new antibacterial therapeutic agents.
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Emami
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Guyet
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Demuris Ltd, Newcastle Biomedicine Bio-Incubators, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Devi
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Ling J
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: Demuris Ltd, Newcastle Biomedicine Bio-Incubators, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Allenby
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Daniel
authors.affiliation: The Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.|Demuris Ltd, Newcastle Biomedicine Bio-Incubators, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Jeff
authors.initials: J
authors.lastname: Errington
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism*; D046928:Peptidoglycan Glycosyltransferase / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D046928:Peptidoglycan Glycosyltransferase; D009713:Nucleotidyltransferases