BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus survival in human blood

Abstract

By the analysis of the recently sequenced genomes of Group B Streptococcus (GBS) we have identified a novel immunogenic adhesin with anti-phagocytic activity, named BibA. The bibA gene is present in 100% of the 24 GBS strains analysed. BibA-specific IgG were found in human sera from normal healthy donors. The putative protein product is a polypeptide of 630 amino acids containing a helix-rich N-terminal domain, a proline-rich region and a canonical LPXTG cell wall-anchoring domain. BibA is expressed on the surface of several GBS strains, but is also recovered in GBS culture supernatants. BibA specifically binds to human C4-binding protein, a regulator of the classic complement pathway. Deletion of the bibA gene severely reduced the capacity of GBS to survive in human blood and to resist opsonophagocytic killing by human neutrophils. In addition, BibA expression increased the virulence of GBS in a mouse infection model. The role of BibA in GBS adhesion was demonstrated by the impaired ability of a bibA knockout mutant strain to adhere to both human cervical and lung epithelial cells. Furthermore, we calculated that recombinant BibA bound to human epithelial cells of distinct origin with an affinity constant of approximately 10(-8) M for cervical epithelial cells. Hence BibA is a novel multifunctional protein involved in both resistance to phagocytic killing and adhesion to host cells. The identification of this potential new virulence factor represents an important step in the development of strategies to combat GBS-associated infections.

Sequence type 1 group B Streptococcus , an emerging cause of invasive disease in adults, evolves by small genetic changes

“…Multiple genes known to contribute to GBS host-pathogen interaction were included among the differentially transcribed genes including srr-1, pilus encoding genes, Alp encoding genes, and bibA, which encodes an cell-surface adhesion critical to GBS survival in human blood ( Fig. 5D) (34). An example of the diversity observed among the studied strains comes from the alp3 gene, whose transcript level was ∼25-fold lower in strains SGBS054 and SGBS046 compared with strain SGBS102 (Fig.…”

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

“…Thus, in strain A909, IS1381 interrupts the ORF encoding the cell-wallanchored surface adhesin BibA (Tettelin et al, 2005). BibA is a multifunctional protein involved in the virulence of S. agalactiae by conferring to the bacteria both an increased resistance to opsonophagocytic killing by human neutrophils, and so a better survival in human blood, and a greater adhesion to host cervical and lung epithelial cells (Santi et al, 2007). In strain 2603V/R, IS1381 interrupts a gene (sag2004/sag2001) predicted to encode a conjugal transfer protein belonging to the ConE/YddE family (Tettelin et al, 2002).…”

Group BStreptococcusPullulanase Crystal Structures in the Context of a Novel Strategy for Vaccine Development

“…The discovery of novel immunogenic virulence factors has also opened new perspectives to tackle GBS-associated infections (4,32). In this context, we considered the characterization of the structural properties of the GBS genes involved in adaptive metabolism of the bacterium to be a necessary step.…”

“…(i) Expression and purification. SAP was cloned into pET21-b and expressed as a C-terminal His-tagged fusion protein in BL21(DE3) Escherichia coli cells, as previously described (32). Bacterial cells were harvested and lysed in buffer A (50 mM sodium phosphate [pH 8.0], 300 mM sodium chloride [NaCl], and 10% glycerol, containing 10 mM imidazole) containing lysozyme (0.25 mg/ml), DNases, and Complete EDTA-free protease inhibitors (Roche).…”