Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

J Biol Chem. 2016 Jul 29;291(31):15985-6000. doi: 10.1074/jbc.M116.726562. Epub 2016 Jun 15.

Abstract

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections.

Keywords: AgI/II family polypeptide; Candida albicans; Streptococcus; adhesin; bacterial adhesion; bacterial pathogenesis; protein conformation; structural model; structure-function; x-ray crystallography.

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism
  • Bacterial Adhesion / physiology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Candida albicans / genetics
  • Candida albicans / metabolism
  • Cell Wall / chemistry*
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Female
  • Humans
  • Lactococcus lactis / chemistry
  • Lactococcus lactis / genetics
  • Lactococcus lactis / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Domains
  • Protein Structure, Secondary
  • Streptococcus agalactiae / chemistry*
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / metabolism
  • Structure-Activity Relationship

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • BspA protein, bacteria
  • Membrane Proteins

Associated data

  • PDB/2WOY
  • PDB/3IOX
  • PDB/5DZ8
  • PDB/5DZ9
  • PDB/5DZA