Moenomycin resistance mutations in Staphylococcus aureus reduce peptidoglycan chain length and cause aberrant cell division

Yuriy Rebets, Tania Lupoli, Yuan Qiao, Kathrin Schirner, Regis Villet, David Hooper, Daniel Kahne, Suzanne Walker

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalACS Chemical Biology
Volume9
Issue number2
DOIs
StatePublished - Feb 21 2014

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Peptidoglycan Glycosyltransferase
Peptidoglycan
Chain length
Cell Division
Staphylococcus aureus
Cells
Mutation
Polysaccharides
Pathogens
Point Mutation
Polymerization
Assays
Catalytic Domain
Polymers
moenomycin
Anti-Bacterial Agents
Defects
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Moenomycin resistance mutations in Staphylococcus aureus reduce peptidoglycan chain length and cause aberrant cell division. / Rebets, Yuriy; Lupoli, Tania; Qiao, Yuan; Schirner, Kathrin; Villet, Regis; Hooper, David; Kahne, Daniel; Walker, Suzanne.

In: ACS Chemical Biology, Vol. 9, No. 2, 21.02.2014, p. 459-467.

Research output: Contribution to journalArticle

Rebets, Yuriy ; Lupoli, Tania ; Qiao, Yuan ; Schirner, Kathrin ; Villet, Regis ; Hooper, David ; Kahne, Daniel ; Walker, Suzanne. / Moenomycin resistance mutations in Staphylococcus aureus reduce peptidoglycan chain length and cause aberrant cell division. In: ACS Chemical Biology. 2014 ; Vol. 9, No. 2. pp. 459-467.
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