Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

Abstract

The Streptococcus pyogenes collagen type I-binding protein Cpa (collagen-binding protein of group A streptococci) expressed by 28 serotypes of group A streptococci has been extensively characterized at the gene and protein levels. Evidence for three distinct families of cpa genes was found, all of which shared a common sequence encoding a 60-amino acid domain that accounted for selective binding to type I collagen. Surface plasmon resonance-based affinity measurements and functional studies indicated that the expression of Cpa was consistent with an attachment role for bacteria to tissue containing collagen type I. A cpa mutant displayed a significantly decreased internalization rate when incubated with HEp-2 cells but had no effect on the host cell viability. By utilizing serum from patients with a positive titer for streptolysin/DNase antibody, an increased anti-Cpa antibody titer was noted for patients with a clinical history of arthritis or osteomyelitis. Taken together, these results suggest Cpa may be a relevant matrix adhesin contributing to the pathogenesis of S. pyogenes infection of bones and joints.

Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration

“…Our results are consistent with other studies showing that RrgA, the pneumococcal homologue of GBS PilA, binds to various ECM proteins including the collagen36, and that minor pilin protein Cpa of Group A Streptococcus (GAS) possess collagen-binding capabilities37. The high sequence similarity between RrgA and pilus adhesins from GAS and GBS (identity level of ~50% with similarity levels beyond 70%) points to the possibility that the three-dimensional fold of these proteins could be highly similar, suggesting that pili components may contribute to a general mechanism of pathogen entry and inflammatory induction.…”

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

“…Most of the linked genes currently identified are clustered within two genomic regions: the emm region itself and the FCT region (125). Genes with a differential presence or absence among tissue-tropic strains include cpa (encoding a type I collagen binding protein) (168), prtF1 (encoding the fibronectin binding protein PrtF1) (169), sof (encoding serum opacity factor, which contains a fibronectin binding domain) (170,171), and prtF2 (encoding the fibronectin binding protein PrtF2) (172). Loci that form discrete phylogenetic lineages, which can then be associated with tissue-specific emm patterns, include the transcriptional regulators mga (a global regulator of numerous virulence factors) (173), rofA and nra (mutually exclusive transcriptional regulators of the genes in the FCT region) (167), and ska (encoding the plasminogen-activating protein streptokinase) (174,175).…”

Region Specific and Worldwide Distribution of Collagen-Binding M Proteins with PARF Motifs among Human Pathogenic Streptococcal Isolates

“…As the streptococcal hyaluronic acid capsule is a potential collagen-binding factor [25], protein-dependent collagen interactions were verified in experiments with hyaluronidase treated bacteria. Several streptococcal factors including M proteins bind collagens [26], [27], [34], [35]. However, based upon a cut-off value of 20% bound ligand [29], only strains that expressed M proteins with a PARF motif bound collagen IV after hyaluronidase treatment (Table 2).…”

“…Nevertheless, it needs to be mentioned that other streptococcal collagen-binding factors exist [25]–[27], [34]; among them M1 protein, that does not have a PARF motif but binds collagen I and VI with high and collagen IV with low affinity. Interestingly, M1 binds to the non-collagenous moiety of collagen VI [26], [27].…”