title: Region specific and worldwide distribution of collagen-binding M proteins with PARF motifs among human pathogenic streptococcal isolates.
abstract: 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.
authors.affiliation: Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Silvana
authors.initials: S
authors.lastname: Reissmann
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gillen
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.forename: René
authors.initials: R
authors.lastname: Bergmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Nerlich
authors.forename: Reena
authors.initials: R
authors.lastname: Rajkumari
authors.forename: Kootallur N
authors.initials: KN
authors.lastname: Brahmadathan
authors.forename: Gursharan S
authors.initials: GS
authors.lastname: Chhatwal
authors.forename: D Patric
authors.initials: DP
authors.lastname: Nitsche-Schmitz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005843:Geography; D006801:Humans; D007194:India; D038622:Internationality; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000302:isolation & purification* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D003094:Collagen