Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions.
Many strains of the important human pathogen Streptococcus pyogenes form aggregates when grown in vitro in liquid medium. The present studies demonstrate that this property is crucial for the adherence, the resistance to phagocytosis and the virulence of S. pyogenes. A conserved sequence of 19 amino acid residues (designated AHP) was identified in surface proteins of common S. pyogenes serotypes. This sequence was found to promote bacterial aggregation through homophilic protein-protein interactions between AHP-containing surface proteins of neighbouring bacteria. A synthetic AHP peptide inhibited S. pyogenes aggregation, reduced the survival of S. pyogenes in human blood and attenuated its virulence in mice. In contrast, mutant bacteria devoid of surface proteins containing AHP-related sequences did not aggregate or adhere to epithelial cells. These bacteria are also rapidly killed in human blood and show reduced virulence in mice, underlining the pathogenic significance of the AHP sequence and S. pyogenes aggregation.
Frick
I M
IM
Department of Cell and Molecular Biology, Sections for Molecular Pathogenesis and Connective Tissue Biology, Lund University, PO Box 94, S-221 00 Lund, Sweden. inga-maria.frick@medkem.lu.se
Mörgelin
M
M
Björck
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010587:Phagocytosis; D013297:Streptococcus pyogenes / Q000378:metabolism / Q000472:pathogenicity*; D014407:Tumor Cells, Cultured; D014774:Virulence
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C064006:protein H, Streptococcus; C014689:streptococcal M protein; D003546:Cysteine Endopeptidases