Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-alpha 1-4-galactose-containing Glycoconjugates CONVERGENT EVOLUTION OF BACTERIAL PATHOGENS TO BINDING OF THE SAME HOST RECEPTOR

: Kouki A, Haataja S, Loimaranta V, Pulliainen AT, Nilsson UJ, Finne J

Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

: 2011

: Journal of Biological Chemistry

: JOURNAL OF BIOLOGICAL CHEMISTRY

: J BIOL CHEM

: 45

: 286

: 45

: 38854

: 38864

: 11

: 0021-9258

DOI: https://doi.org/10.1074/jbc.M111.260992(external)

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-alpha 1-4-galactose (Gal alpha 1-4Gal)-containing host receptors. A functionally unknown S. suis cell wall protein (SSU0253), designated here as SadP (streptococcal adhesin P), was identified using a Gal alpha 1-4Gal-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 Gal alpha 1-4Gal-dependent binding. The adhesin gene sadP was cloned and expressed in Escherichia coli. Characterization of its binding specificity showed that SadP recognizes Gal alpha 1-4Gal-oligosaccharides and binds its natural glycolipid receptor, GbO(3) (CD77). The N terminus of SadP was shown to contain a Gal alpha 1-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 Gal alpha 1-4Gal disaccharide. The SadP and E. coli P adhesins represent a unique example of convergent evolution toward binding to the same host receptor structure.