title: Adherence and internalization of Streptococcus gordonii by epithelial cells involves beta1 integrin recognition by SspA and SspB (antigen I/II family) polypeptides.
abstract: Streptococcus gordonii is a commensal bacterium that colonizes the hard and soft tissues present in the human mouth and nasopharynx. The cell wall-anchored polypeptides SspA and SspB expressed by S. gordonii mediate a wide range of interactions with host proteins and other bacteria. In this article we have determined the role of SspA and SspB proteins, which are members of the streptococcal antigen I/II (AgI/II) adhesin family, in S. gordonii adherence and internalization by epithelial cells. Wild-type S. gordonii DL1 expressing AgI/II polypeptides attached to and was internalized by HEp-2 cells, whereas an isogenic AgI/II- mutant was reduced in adherence and was not internalized. Association of S. gordonii DL1 with HEp-2 cells triggered protein tyrosine phosphorylation but no significant actin rearrangement. By contrast, Streptococcus pyogenes A40 showed 50-fold higher levels of internalization and this was associated with actin polymerization and interleukin-8 upregulation. Adherence and internalization of S. gordonii by HEp-2 cells involved beta1 integrin recognition but was not fibronectin-dependent. Recombinant SspA and SspB polypeptides bound to purified human alpha5beta1 integrin through sequences present within the NAV (N-terminal) region of AgI/II polypeptide. AgI/II polypeptides blocked interactions of S. gordonii and S. pyogenes with HEp-2 cells, and S. gordonii DL1 cells expressing AgI/II proteins inhibited adherence and internalization of S. pyogenes by HEp-2 cells. Conversely, S. gordonii AgI/II- mutant cells did not inhibit internalization of S. pyogenes. The results suggest that AgI/II proteins not only promote integrin-mediated internalization of oral commensal streptococci by host cells, but also potentially influence susceptibility of host tissues to more pathogenic bacteria.
authors.affiliation: Oral Microbiology Unit, Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Nobbs
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Shearer
authors.forename: Mirva
authors.initials: M
authors.lastname: Drobni
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jepson
authors.forename: Howard F
authors.initials: HF
authors.lastname: Jenkinson
mesh_terms: D018829:Adhesins, Bacterial / Q000302:isolation & purification / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics; D007830:Larynx / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D013291:Streptococcus / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016209:Interleukin-8; D008562:Membrane Glycoproteins; C055764:S-layer proteins; C082314:SspA protein, bacteria; C068465:salivary agglutinin receptor, Streptocococcus