The surface (S-) layer is a virulence factor of Bacteroides forsythus

<jats:p> <jats:italic>Bacteroides forsythus</jats:italic> has emerged as a crucial periodontal pathogen with possible implications for systemic disease. The aim of this study was to isolate the S-layer from <jats:italic>B. forsythus</jats:italic> and examine its virulence potential as a part of efforts to characterize virulence factors of <jats:italic>B. forsythus</jats:italic>. The role of the S-layer in the haemagglutinating and adherent/invasive activities was evaluated. It was observed that the S-layer alone was able to mediate haemagglutination. In adherent and invasive studies, transmission electron microscopy clearly revealed that <jats:italic>B. forsythus</jats:italic> cells were able to attach to and invade KB cells, showing the formation of a microvillus-like extension around adherent and intracellular bacteria. The quantitative analysis showed that five different <jats:italic>B. forsythus</jats:italic> strains exhibited attachment (1·9–2·3 %) and invasion (0·4–0·7 %) capabilities. It was also observed through antibody inhibition assays that adherent/invasive activities of <jats:italic>B. forsythus</jats:italic> are mediated by the S-layer. Furthermore, an <jats:italic>in vivo</jats:italic> immunization study adopting a murine abscess model was used to prove that the S-layer is involved in the infectious process of abscess formation. While mice immunized with purified S-layer and <jats:italic>B. forsythus</jats:italic> whole cells did not develop any abscesses when challenged with viable <jats:italic>B. forsythus</jats:italic> cells, unimmunized mice developed abscesses. Collectively, the data obtained from these studies indicate that the S-layer of <jats:italic>B. forsythus</jats:italic> is a virulence factor.</jats:p>