Related Experiment Videos
Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions
I M Frick1, M Mörgelin, L Björck
1Department 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
Abstract:
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.
Insights
Streptococcus pyogenes aggregation, driven by the AHP surface protein sequence, is vital for its virulence. Inhibiting this sequence reduces bacterial survival and pathogenicity.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Streptococcus pyogenes, a significant human pathogen, often forms aggregates in liquid cultures.
- Bacterial aggregation is increasingly recognized as a factor in pathogen virulence and host interaction.
Purpose of the Study:
- To investigate the role of bacterial aggregation in Streptococcus pyogenes pathogenesis.
- To identify and characterize the molecular mechanisms underlying Streptococcus pyogenes aggregation.
Main Methods:
- Identification of a conserved 19-amino acid sequence (AHP) in S. pyogenes surface proteins.
- Analysis of AHP function through synthetic peptide inhibition and mutant generation.
- Assessment of bacterial aggregation, adherence, resistance to phagocytosis, and virulence in mouse models.
Main Results:
- The AHP sequence promotes bacterial aggregation via homophilic protein-protein interactions.
- Synthetic AHP peptide inhibited aggregation, reduced S. pyogenes survival in blood, and attenuated virulence in mice.
- Mutant bacteria lacking AHP-related sequences showed impaired aggregation, reduced adherence to epithelial cells, and decreased virulence.
Conclusions:
- The AHP sequence is critical for Streptococcus pyogenes aggregation.
- Bacterial aggregation mediated by the AHP sequence is essential for S. pyogenes adherence, resistance to phagocytosis, and overall virulence.
- Targeting the AHP sequence offers a potential strategy to combat S. pyogenes infections.