Streptococcal β Protein Has Separate Binding Sites for Human Factor H and IgA-Fc

Abstract

The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the ␤ protein, is known to bind human IgA-Fc. Here, we show that the ␤ protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing ␤ protein but not to an isogenic ␤-negative mutant. This binding was due to a direct interaction between ␤ and FH, as shown by experiments with purified proteins. Inhibition tests and studies with ␤ fragments demonstrated that FH and IgA-Fc bind to separate and nonoverlapping regions in ␤. Heparin, a known ligand for FH, specifically inhibited the binding between ␤ and FH, suggesting that FH has overlapping binding sites for ␤ and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that ␤-expressing GBS may use bound FH to evade complement attack. The finding that ␤ protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.

Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

“…It reveals that FbaA potentially promote the entry of GAS into human epithelial cells to shield the bacterium from antibiotics and the immune system. The ability of bacterial pathogens to evade complement attack and opsonophagocytosis is often influenced or dictated by a pathogen's ability to bind complement regulatory proteins (14,15). FbaA, the first non-M-like protein of GAS, is shown to bind these complement regulatory factors.…”

Dual Roles of PspC, a Surface Protein of Streptococcus pneumoniae, in Binding Human Secretory IgA and Factor H

“…The Sir protein of Streptococcus pyogenes is able to bind both Ig and C4BP at separate sites within the N-terminal fragment of the molecule (36). Likewise, ␤ protein of group B Streptococcus binds sIgA at the N terminus, whereas the C terminus of this protein is involved in FH binding (37).…”

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

“…IS861 was found to be present in 59 to 76.9 % of strains of human origin and in 28.7 to 37 % of bovine isolates (Dmitriev et al, 2003;Héry-Arnaud et al, 2005;Shakleina et al, 2004). This IS is highly associated (94 % of the tested strains) with human isolates containing the bac gene which encodes a surface protein that is able to bind the Fc portion of IgA and the factor H. Like the capsule, the Bac protein (also called C protein b antigen) is thought to help bacteria to escape from the immune response, by inhibiting complement attack (Areschoug et al, 2002;Kong et al, 2006).…”