In this report, we identified 11 proteins containing histidine triad motifs from S. suis 2, and three of them were revealed to have the characteristics of histidine triad family proteins. Both SSU05_1267 and SSU05_1577 are homologous to InlA. SSU05_1577 also shows similarity to Slr and Blr, two InlA-like proteins of S. pyogenes and Streptococcus agalactiae, with the histidine triad motifs in the N-terminal region and leucine-rich repeats (LRRs) in

the C-terminal region. Although both Slr and Blr have been shown to be cell surface-associated proteins, their biological function and protective capacity are poorly understood (Reid et al., 2003; Waldemarsson et al., 2006). HtpS, Z-VAD-FMK supplier one of the three histidine triad family proteins of S. suis 2 described in this report, is homologous to HtpA and PhtD, which have been shown to be protective antigens (Adamou et al., 2001; Kunitomo et al., 2008). The htpS gene is distributed in 83% (29/35) of the tested S. suis reference strains of different serotypes and highly conserved in the four genome-sequenced S. suis 2 strains of different geographic origins. FCM and Western blotting confirmed that HtpS is a cell surface-associated protein. It is worth noting that although no palpable TSA HDAC purchase LPXTG motif was present in HtpS, or Pht proteins and HtpA, this family of proteins

could be exposed to the cell surface by an unknown mechanism. However, it was predicted that N-terminal hydrophobic leader sequences of this protein

family are involved in targeting them to the bacterial cell surface (Adamou et al., 2001). Considering that recent reports have proposed that the histidine triad protein family protein HtpA was associated with zinc transport (Kunitomo et al., 2008), and that Pht proteins were involved in C3 deposition by means of directly binding to complement factor H (Ogunniyi et al., 2009), histidine triad protein family proteins may play important roles in the physiology and pathogenesis of Streptococcus. Immunological data showed that HtpS reacted strongly with convalescent-phase sera from pigs infected by S. suis 2, indicating that HtpS is expressed and exposed in vivo, and could be recognized by the immune system and elicit a host response during the natural infection of S. suis 2. We also observed that immunization with rHtpS could Urocanase elicit specific antibody responses in mice. It is believed that antibodies specific to external antigens of microbial pathogens are critical factors of humoral immunity in the protection of the host against invasive diseases (Lancefield et al., 1975; Matthews & Burnie, 1998; Corbeil, 2002; Glatman-Freedman, 2006; Campos et al., 2008; Granoff, 2009). Our experiment on C3 deposition demonstrated that antibodies to HtpS increased C3 deposition on S. suis 2. This could be considered to be the reason why the survival of S. suis 2 was decreased in whole blood containing anti-HtpS sera.