Adherence and internalization of Streptococcus gordonii by epithelial cells involves β1 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 β1 integrin recognition but was not fibronectin-dependent. Recombinant SspA and SspB polypeptides bound to purified human α5β1 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. © 2006 The Authors; Journal compilation. © 2006 Blackwell Publishing Ltd.