Isolation, structural characterization, and immunological evaluation of a high-molecular-weight exopolysaccharide from Staphylococcus aureus

Carbohydr Res. 2003 Apr 22;338(9):903-22. doi: 10.1016/s0008-6215(03)00045-4.

Abstract

Colonization of implanted medical devices by coagulase-negative staphylococci such as Staphylococcus epidermidis is mediated by the bacterial polysaccharide intercellular adhesin (PIA), a polymer of beta-(1-->6)-linked glucosamine substituted with N-acetyl and O-succinyl constituents. The icaADBC locus containing the biosynthetic genes for production of PIA has been identified in both S. epidermidis and S. aureus. Whereas it is clear that PIA is a constituent that contributes to the virulence of S. epidermidis, it is less clear what role PIA plays in infection with S. aureus. Recently, identification of a novel polysaccharide antigen from S. aureus termed poly N-succinyl beta-(1-->6)-glucosamine (PNSG) has been reported. This polymer was composed of the same glycan backbone as PIA but was reported to contain a high proportion of N-succinylation rather than acetylation. We have isolated a glucosamine-containing exopolysaccharide from the constitutive over-producing MN8m strain of S. aureus in order to prepare polysaccharide-protein conjugate vaccines. In this report we demonstrate that MN8m produced a high-molecular-weight (>300,000 Da) polymer of beta-(1-->6)-linked glucosamine containing 45-60% N-acetyl, and a small amount of O-succinyl (approx 10% mole ratio to monosaccharide units). By detailed NMR analyses of polysaccharide preparations, we show that the previous identification of N-succinyl was an analytical artifact. The exopolysaccharide we have isolated is active in in vitro hemagglutination assays and is immunogenic in mice when coupled to a protein carrier. We therefore conclude that S. aureus strain MN8m produces a polymer that is chemically and biologically closely related to the PIA produced by S. epidermidis.

MeSH terms

  • Animals
  • Carbohydrate Conformation
  • Chromatography, Gel
  • Enzyme-Linked Immunosorbent Assay
  • Hemagglutination Tests
  • Levulinic Acids / analysis
  • Levulinic Acids / chemistry
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Weight
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology*
  • Polysaccharides, Bacterial / isolation & purification*
  • Staphylococcus aureus / chemistry*

Substances

  • Levulinic Acids
  • Polysaccharides, Bacterial
  • levulinic acid