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Identification of a streptococcal octapeptide motif involved in acute rheumatic fever

In English

Författare

  • Katrin Dinkla
  • D. Patric Nitsche-Schmitz
  • Vanessa Barroso
  • Silvana Reissmann
  • Helena Linge
  • Inga-Maria Frick
  • Manfred Rohde
  • Gursharan S. Chhatwal

Summary, in English

Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails. Examination of such strains revealed the presence of M-like surface proteins that bind human collagen. Using a peptide array and recombinant proteins with targeted amino acid substitutions, we could demonstrate that formation of collagen complexes during streptococcal infections depends on an octapeptide motif, which is present in collagen binding M and M-like proteins of different beta-hemolytic streptococcal species. Mice immunized with streptococcal proteins that contain the collagen binding octapeptide motif developed high serum titers of anti-collagen antibodies. In sera of rheumatic fever patients such a collagen autoimmune response was accompanied by specific reactivity against the collagen-binding proteins, linking the observed effect to clinical cases. Taken together, the data demonstrate that the identified octapeptide motif through its action on collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication of streptococci that express proteins with the collagen binding motif appears advisable for controlling rheumatic fever.

Avdelning/ar

Publiceringsår

2007

Språk

Engelska

Sidor

18686-18693

Publikation/Tidskrift/Serie

Journal of Biological Chemistry

Volym

282

Issue

26

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Biochemistry and Molecular Biology

Ämne

  • Infectious Medicine

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1083-351X