Region specific and worldwide distribution of collagen-binding M proteins with PARF motifs among human pathogenic streptococcal isolates

• Published in: PloS one Vol. 7; no. 1; p. e30122
• Main Authors: Reissmann, Silvana, Gillen, Christine M, Fulde, Marcus, Bergmann, René, Nerlich, Andreas, Rajkumari, Reena, Brahmadathan, Kootallur N, Chhatwal, Gursharan S, Nitsche-Schmitz, D Patric
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.01.2012; Public Library of Science (PLoS)
• Subjects: Adhesins; Amino Acid Motifs; Amino Acid Sequence; Amino acids; Antibiotics; Autoimmunity; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding; Biology; Clinical isolates; Collagen; Collagen - metabolism; Epidemiology; Fever; Geography; Health aspects; Humans; India; Infection; Infections; Internationality; M protein; Medicine; Molecular Sequence Data; Multilocus sequence typing; Pathogenesis; Peptides; Protein Binding; Protein Structure, Tertiary; Proteins; Recombinant Proteins - metabolism; Rheumatic fever; Risk analysis; Risk factors; Streptococcus; Streptococcus infections; Streptococcus pyogenes; Streptococcus pyogenes - isolation & purification; Streptococcus pyogenes - metabolism; Vaccines; India; Mumbai India; Norway; Germany; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0030122

Some of the variety of Streptococcus pyogenes and Streptococcus dysgalactiae ssp. equisimilis (SDSE) M proteins act as collagen-binding adhesins that facilitate acute infection. Moreover, their potential to trigger collagen autoimmunity has been implicated in the pathogenesis of acute rheumatic fever and attributed to a collagen-binding motif called PARF (peptide associated with rheumatic fever). For the first time we determine the rate of clinical isolates with collagen-binding M proteins that use a PARF motif (A/T/E)XYLXX(L/F)N in a defined geographic region, Vellore in South India. In this region both, incidence of streptococcal infections and prevalence of acute rheumatic fever are high. M proteins with PARF motif conferred collagen-binding activity to 3.9% of 153 S. pyogenes and 10.6% of 255 SDSE clinical isolates from Vellore. The PARF motif occurred in three S. pyogenes and 22 SDSE M protein types. In one of the S. pyogenes and five of the SDSE M proteins that contained the motif, collagen-binding was impaired, due to influences of other parts of the M protein molecule. The accumulated data on the collagen binding activity of certain M protein types allowed a reanalysis of published worldwide emm-typing data with the aim to estimate the rates of isolates that bind collagen via PARF. The results indicate that M proteins, which bind collagen via a PARF motif, are epidemiologically relevant in human infections, not only in Vellore. It is imperative to include the most relevant collagen-binding M types in vaccines. But when designing M protein based vaccines it should be considered that collagen binding motifs within the vaccine antigen remain potential risk factors.