Identification of active variants of PARF in human pathogenic group C and group G streptococci leads to an amended description of its consensus motif.
Certain streptococcal M proteins bind collagen via an octapeptide motif that is located in their hypervariable N-terminal region. The interaction with this extracellular matrix protein enhances adhesion to the host tissue and thereby facilitates infection. Moreover, it has the side effect of eliciting collagen autoimmune responses, a phenomenon which is also observed in patients with acute rheumatic fever. Therefore, the octapeptide motif was named peptide associated with rheumatic fever (PARF). Only a comprehensive characterization of the collagen-binding M proteins and their collagen-binding motifs will allow the investigation of their associations with certain streptococcal infections and their sequelae. Therefore, a collection of Streptococcus dysgalactiae equisimilis strains that were isolated from infected humans was examined, in order to identify collagen-binding proteins and motifs. Strains that bound collagen independent of a hyaluronic acid capsule belonged to 7 distinct types of the emm gene, which codes for the M protein (emm types). Only one of these emm types was previously described as collagen-binding. Five possessed a PARF sequence. The other 2 emm types stC2sk.0 and stG2574 had PARF-like motifs that diverged from the previously described consensus sequence AXYLZZLN but were able to induce collagen autoimmunity when injected into mice. The results led to the amended PARF consensus (A/E/T)XYLXXLN. Moreover, they demonstrate a predictive power regarding collagen-binding and elicitation of collagen autoimmunity, indicating that PARF may be one of the markers for strains that cause collagen-dependent acute rheumatic fever.
Barroso
Vanessa
V
Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Rohde
Manfred
M
Davies
Mark R
MR
Gillen
Christine M
CM
Nitsche-Schmitz
D Patric
DP
Dinkla
Katrin
K
Chhatwal
Gursharan S
GS
D020816:Amino Acid Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000502:physiology*; D015551:Autoimmunity; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D003094:Collagen / Q000276:immunology* / Q000378:metabolism; D016384:Consensus Sequence; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D016415:Sequence Alignment; D013290:Streptococcal Infections / Q000382:microbiology; D013291:Streptococcus / Q000472:pathogenicity*; D020349:Surface Plasmon Resonance; D037521:Virulence Factors / Q000235:genetics* / Q000502:physiology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors; C014689:streptococcal M protein; D003094:Collagen