Identification of a streptococcal octapeptide motif involved in acute rheumatic fever.
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.
Dinkla
Katrin
K
Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Nitsche-Schmitz
D Patric
DP
Barroso
Vanessa
V
Reissmann
Silvana
S
Johansson
Helena M
HM
Frick
Inga-Maria
IM
Rohde
Manfred
M
Chhatwal
Gursharan S
GS
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D024141:Collagen Type IV / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D012213:Rheumatic Fever / Q000276:immunology* / Q000382:microbiology*; D013047:Specific Pathogen-Free Organisms; D013291:Streptococcus / Q000276:immunology* / Q000472:pathogenicity / Q000648:ultrastructure; D020349:Surface Plasmon Resonance; D014774:Virulence
D000907:Antibodies, Bacterial; D001323:Autoantibodies; D001426:Bacterial Proteins; D015415:Biomarkers; D024141:Collagen Type IV; D010446:Peptide Fragments