Fhb, a Novel Factor H-Binding Surface Protein, Contributes to the Antiphagocytic Ability and Virulence of Streptococcus suis

Abstract

<jats:title>ABSTRACT</jats:title><jats:p><jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Streptococcus suis</jats:named-content>serotype 2 is a Gram-positive bacterium that causes sepsis and meningitis in piglets and humans. The mechanisms of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. suis</jats:named-content>serotype 2 invasive disease are not well understood. The surface proteins of pathogens usually play important roles in infection and bacterium-host interactions. Here, we identified a novel surface protein that contributed significantly to the virulence of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. suis</jats:named-content>serotype 2 in a piglet infection model. This protein showed little similarity to other reported proteins and exhibited strong binding activity to human factor H (hFH). It was designated Fhb (factor H-binding protein). The<jats:italic>fhb</jats:italic>genes found in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. suis</jats:named-content>serotypes 1, 2, 4, 7, and 9 exhibited molecular polymorphism. Fhb possessed two proline-rich repeat sequences and XPZ domains, and one repeat sequence exhibited a high homology to Bac, an IgA-binding protein of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Streptococcus agalactiae</jats:named-content>. Evidence strongly indicated that<jats:italic>fhb</jats:italic>-deficient mutants had diminished phagocytosis resistance in bactericidal assays. In addition, Fhb plays important roles in complement-mediated immunity by interacting with hFH. These findings indicated that Fhb is a crucial surface protein contributing to the virulence of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. suis</jats:named-content>, with important functions in evading innate immune defenses by interaction with host complement regulatory factor hFH.</jats:p>

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb

“…shown in our previous study (19). In addition, the levels of C3b/ iC3b deposited on C-Fhb⌬II were not rescued because of deletion of Fhb II (Fig.…”

“…Presence of Fhb in the Culture Supernatant and on the Bacterial Surface-Fhb has been demonstrated to be a surface protein with an LPXTG motif (19,22). However, the protein is possibly also present in culture supernatants because some surface proteins are released from the bacterial cell wall into the culture supernatant (23).…”

“…C3b/C3d-binding Site in the Fhb Protein-Fhb displayed low similarity to other function-known proteins (19), so determining the region of Fhb responsible for binding to C3 may help elucidate its role in the pathogenesis of S. suis. By ligand blotting, we found that domain II of Fhb is responsible for the interaction with C3b/C3d as FH (Fig.…”

“…Also in S. aureus, secretion of C3b-binding proteins (Ecb and Efb) can result in the blocking of C3 convertases of the alternative pathway, which enhances complement evasion (17,18). In our previous study (19), FH binding to the surface of S. suis 2 was reported to involve Fhb, a surface protein with a proline-rich repeat domain and LPXTG motif. Moreover, activation of human complement by S. suis mainly via the alternative pathway and FH bound to the Fhb protein inhibits complement activation in human blood (19).…”

“…In our previous study (19), FH binding to the surface of S. suis 2 was reported to involve Fhb, a surface protein with a proline-rich repeat domain and LPXTG motif. Moreover, activation of human complement by S. suis mainly via the alternative pathway and FH bound to the Fhb protein inhibits complement activation in human blood (19).…”