Conservation of salivary glycoprotein-interacting and human immunoglobulin G-cross-reactive domains of antigen I/II in oral streptococci

Abstract

In this study we localized more precisely the salivary glycoprotein-interacting and the human immunoglobulin G (hIgG)-cross-reacting domains on the SR molecule, an antigen I/Il-related protein from S. mutans serotype f. Mapping of the SR molecule with polypeptides expressed by subclones covering the entire molecule and with synthetic peptides demonstrates that the salivary glycoprotein-binding domain is located in the N-terminal alanine-rich repeats of the SR molecule. In order to investigate the degree of conservation of both regions in various oral streptococci, we tested the reactivity of 8 representative strains of the mutans group and 11 nonmutans oral Streptococcus strains (S. anginosus, S. milleri, S. consteUlatus, S. intermedius, S. mitis, S. sanguis, S. gordonii, S. salivarius, and S. mitis strains) with antipeptide antibodies in a whole-cell enzyme linked immunosorbent assay together with colony hybridization analysis using DNA probes designed to map these two regions. All the mutans group strains except S. rattus and the 11 nonmutans streptococcal strains showed a high conservation of the C-terminal part of the SR molecule, especially the hIgG-cross-reacting domain, and less homology for the N-terminal salivary glycoprotein-binding region. Almost all of the sera from patients with rheumatic disease reacted strongly with SR from S. mutans serotype f, PI from S. mutans serotype c, and four peptides located in the hIgG-cross-reacting region and not with peptides located at the C and N termini and in the proline-rich repeats. These results confirm that epitopes located within this region are immunogenic in humans and could lead to the synthesis of natural anti-IgG antibodies.

Tandem genes encode cell‐surface polypeptides SspA and SspB which mediate adhesion of the oral bacterium Streptococcus gordonii to human and bacterial receptors

“…160 kDa in size and have been given a variety of names according to the strains and species in which they were originally identified. They include antigen 1/ 11 (Russell and Lehner, 1978), antigen B (Russell, 1979), P i (Forester et al, 1983), SpaP (Kelly et a/., 1989), PAC (Okahashi et a/., 1989), and MSL-1 (Demuth et a/., 1990b) from Streptococcus mutans serotype c, SR protein (Ogier et a/., 1990) from S. mutans serotype f, and SpaA (LaPolla et al, 1991) and PAg (Tokuda et a/., 1991) from Sfreptococcus sobrinus serotype g. There is good evidence that these proteins are involved in adhesion of mutans streptococci to salivary glycoproteins either in fluid phase Brady et a/., 1992;Moisset et a/., 1994) or adsorbed to hydroxylapatite beads in experimental salivary pellicles (Koga eta/., 1990;Munro eta/., 1993). Antibodies to antigen 1/11 polypeptides in human serum and saliva may be protective against mutans streptococcal colonization (Ma eta/., 1990;Hajishengallis eta/., 1992).…”

Cell surface protein receptors in oral streptococci

“…The similarities in amino acid sequence be- Table 1 Two families of cell-surface polypeptide receptors in oral streptococci tween these various polypeptides and some functional implications have been discussed elsewhere [15]. In essence, the A region repeats are moderately well conserved across species, the sequence between A and PR1 is highly variable, and a sequence of roughly 200 amino acids C-terminal to PR1 is highly conserved [17,18]. Adherenceblocking experiments utilizing antibodies to synthetic peptides [18], monoclonal antibodies to defined regions [19] and recombinant polypeptide segments [20,21] all strongly implicate the A region in binding of antigen I/II to salivary glycoproteins.…”

“…In essence, the A region repeats are moderately well conserved across species, the sequence between A and PR1 is highly variable, and a sequence of roughly 200 amino acids C-terminal to PR1 is highly conserved [17,18]. Adherenceblocking experiments utilizing antibodies to synthetic peptides [18], monoclonal antibodies to defined regions [19] and recombinant polypeptide segments [20,21] all strongly implicate the A region in binding of antigen I/II to salivary glycoproteins. The highly conserved region may be involved in protein antigen assembly [21] and contains epitopes in common with human immunoglobulin G [18].…”

“…Antibodies raised to a 17-residue peptide from within the A region of SR polypeptide bind to whole cells of S. mutans, but not S. sobrinus or S. gordonff, suggesting that the peptide epitopes are both surface-exposed and unique [18]. Conversely, antibodies to peptides derived from the conserved region bound to cells of all other oral streptococci tested [18]. Therefore a current notion is that the A region not only may contain the binding domain(s) for salivary glycoproteins, but also may provide binding specificity.…”

“…3). Since the a region of the LraI family is predicted from several algorithms to have high surface probability, and the A region segments of antigen I/II polypeptides are likely to be surface-exposed [ 15,18], it is possible that ScaA and SSP5 present common epitopes. Any functional significance in this structural similarity must await experimental analysis.…”