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Keywords:

  • Streptococcal M protein;
  • Virulence;
  • Group C streptococcus;
  • Plasma protein binding;
  • Cross-reactivity;
  • Vimentin;
  • Keratin

Abstract

Besides group A (GAS), Lancefield group C β-haemolytic streptococci (GCS) have been implicated as a causative agent in outbreaks of purulent pharyngitis. In this study we have investigated a class CI M protein of a Streptococcus dysgalactiae human wound isolate designated MC. MC shares similar properties with M proteins of GAS. It contributes to the virulence of the investigated GCS strain as revealed by in vivo phagocytosis in chicken embryos. Further, MC showed multiple binding to the human plasma proteins fibrinogen, albumin, plasminogen, IgA and all subclasses of IgG. Until now, an M protein, especially from a group C strain, with such a multiple binding behaviour has not been described. Immunoblot experiments with 150 patient sera, having a rheumatoid factor titre >1:256, revealed that 26% of these sera showed serological cross-reactivity between a 68-kDa cartilage protein and the N-terminal part of MC. Only 8% of the sera of healthy patients showed this property. In additional, MC also cross-reacted with antibodies recognising epidermal keratins. The cross-reacting 68-kDa protein from cartilage was different from human serum albumin, but was recognised with anti-vimentin immune serum. The MC was cloned and the gene sequenced. By using PCR, recombinant gene fragments encoding characteristic peptide fragments of MC were expressed in Escherichia coli. The peptides were used to map the binding sites for plasma proteins and to locate the cross-reacting epitopes on the MC molecule. In consequence, sequence alignments revealed that MC shared homologous regions with vimentin and different keratins. Our data, obtained with MC, suggest that not only infections with GAS but also infections with GCS and possibly GGS (the latter species can also produce class CI M-like proteins) may be responsible for the formation of streptococcal-associated sequel diseases.