globotriaosylceramide and Swine-Diseases

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.

Topics: Adhesins, Bacterial; Animals; Cloning, Molecular; Disaccharides; Escherichia coli; Evolution, Molecular; Gene Expression; Glycoproteins; Humans; Mass Spectrometry; Mutation; Protein Binding; Proteomics; Streptococcus suis; Swine; Swine Diseases; Trihexosylceramides

Oral infection with enterohemorrhagic Escherichia coli (EHEC) may cause severe enteritis, followed in up to 10% of cases by an extraintestinal complication, the hemolytic uremic syndrome (HUS). HUS is characterized by a triad of symptoms: anemia, thrombocytopenia, and acute renalfailure due to thrombotic microangiopathy. EHEC produces several virulence factors, among which a family of phage-encoded cytotoxins, called Shiga toxin 1 and Shiga toxin 2, seems to be most important. However, since an appropriate animal model is not available, pathogenicity of these emerging enteric pathogens is still poorly understood. Germ-free gnotobiotic piglets infected orally with an O1577:H7 or an O26:H11 EHEC wild-type isolate, both producing Shiga toxin 2, developed intestinal and extraintestinal manifestations of EHEC disease, including thrombotic microangiopathy in the kidneys, the morphologic hallmark of HUS in humans. Thus, gnotobiotic piglets are suitable to further study the pathophysiology of EHEC-induced HUS. It can be expected that data obtainedfrom this animal model will improve our current standard of knowledge about this emerging infectious disease.

Topics: Animals; Child, Preschool; Digestive System; Disease Models, Animal; Endothelium, Vascular; Escherichia coli Infections; Escherichia coli O157; Female; Germ-Free Life; Hemolytic-Uremic Syndrome; Humans; Immunohistochemistry; Kidney; Microcirculation; Purpura, Thrombotic Thrombocytopenic; Shiga Toxin 2; Swine; Swine Diseases; Trihexosylceramides