title: Moenomycin resistance mutations in Staphylococcus aureus reduce peptidoglycan chain length and cause aberrant cell division.
abstract: Staphylococcus aureus is a Gram-positive pathogen with an unusual mode of cell division in that it divides in orthogonal rather than parallel planes. Through selection using moenomycin, an antibiotic proposed to target peptidoglycan glycosyltransferases (PGTs), we have generated resistant mutants containing a single point mutation in the active site of the PGT domain of an essential peptidoglycan (PG) biosynthetic enzyme, PBP2. Using cell free polymerization assays, we show that this mutation alters PGT activity so that much shorter PG chains are made. The same mutation in another S. aureus PGT, SgtB, has a similar effect on glycan chain length. Moenomycin-resistant S. aureus strains containing mutated PGTs that make only short glycan polymers display major cell division defects, implicating PG chain length in determining bacterial cell morphology and division site placement.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Rebets
authors.forename: Tania
authors.initials: T
authors.lastname: Lupoli
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schirner
authors.forename: Regis
authors.initials: R
authors.lastname: Villet
authors.forename: David
authors.initials: D
authors.lastname: Hooper
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahne
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D008958:Models, Molecular; D009844:Oligosaccharides / Q000494:pharmacology*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D046928:Peptidoglycan Glycosyltransferase / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009844:Oligosaccharides; D010457:Peptidoglycan; D046928:Peptidoglycan Glycosyltransferase; C419802:moenomycin