Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions

Many strains of the important human pathogen Streptococcus pyogenes form ag gregates when grown in vitro in liquid medium. The present studies demonstr ate that this property is crucial for the adherence, the resistance to phag ocytosis and the virulence of S. pyogenes. A conserved sequence of 19 amino acid residues (designated AHP) was identified in surface proteins of commo n S. pyogenes serotypes. This sequence was found to promote bacterial aggre gation through homophilic protein-protein interactions between AHP-containi ng surface proteins of neighbouring bacteria. A synthetic AHP peptide inhib ited S. pyogenes aggregation, reduced the survival of S. pyogenes in human blood and attenuated its virulence in mice. In contrast, mutant bacteria de void of surface proteins containing AHP-related sequences did not aggregate or adhere to epithelial cells. These bacteria are also rapidly killed in h uman blood and show reduced virulence in mice, underlining the pathogenic s ignificance of the AHP sequence and S. pyogenes aggregation.