Identification of a novel streptococcal adhesin P (SadP) protein recognizing galactosyl-α1-4-galactose-containing glycoconjugates: convergent evolution of bacterial pathogens to binding of the same host receptor

J Biol Chem. 2011 Nov 11;286(45):38854-64. doi: 10.1074/jbc.M111.260992. Epub 2011 Sep 9.

Abstract

Bacterial adhesion is often a prerequisite for infection, and host cell surface carbohydrates play a major role as adhesion receptors. Streptococci are a leading cause of infectious diseases. However, only few carbohydrate-specific streptococcal adhesins are known. Streptococcus suis is an important pig pathogen and a zoonotic agent causing meningitis in pigs and humans. In this study, we have identified an adhesin that mediates the binding of S. suis to galactosyl-α1-4-galactose (Galα1-4Gal)-containing host receptors. A functionally unknown S. suis cell wall protein (SSU0253), designated here as SadP (streptococcal adhesin P), was identified using a Galα1-4Gal-containing affinity matrix and LC-ESI mass spectrometry. Although the function of the protein was not previously known, it was recently identified as an immunogenic cell wall protein in a proteomic study. Insertional inactivation of the sadP gene abolished S. suis Galα1-4Gal-dependent binding. The adhesin gene sadP was cloned and expressed in Escherichia coli. Characterization of its binding specificity showed that SadP recognizes Galα1-4Gal-oligosaccharides and binds its natural glycolipid receptor, GbO(3) (CD77). The N terminus of SadP was shown to contain a Galα1-Gal-binding site and not to have apparent sequence similarity to other bacterial adhesins, including the E. coli P fimbrial adhesins, or to E. coli verotoxin or Pseudomonas aeruginosa lectin I also recognizing the same Galα1-4Gal disaccharide. The SadP and E. coli P adhesins represent a unique example of convergent evolution toward binding to the same host receptor structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial* / chemistry
  • Adhesins, Bacterial* / genetics
  • Adhesins, Bacterial* / metabolism
  • Animals
  • Cloning, Molecular
  • Disaccharides* / chemistry
  • Disaccharides* / genetics
  • Disaccharides* / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Evolution, Molecular*
  • Gene Expression
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Mass Spectrometry
  • Mutation
  • Protein Binding
  • Proteomics
  • Streptococcus suis* / chemistry
  • Streptococcus suis* / genetics
  • Streptococcus suis* / metabolism
  • Swine
  • Swine Diseases
  • Trihexosylceramides / chemistry*
  • Trihexosylceramides / metabolism*

Substances

  • Adhesins, Bacterial
  • Disaccharides
  • Glycoproteins
  • Trihexosylceramides
  • 4-O-alpha-D-galactopyranosyl-D-galactose
  • globotriaosylceramide