BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus survival in human blood.
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.
Santi
Isabella
I
Novartis Vaccines and Diagnostics Srl, Via Fiorentina 1, 53100, Siena, Italy.
Scarselli
Maria
M
Mariani
Massimo
M
Pezzicoli
Alfredo
A
Masignani
Vega
V
Taddei
Annarita
A
Grandi
Guido
G
Telford
John L
JL
Soriani
Marco
M
D018829:Adhesins, Bacterial / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion; D050716:Complement C4b-Binding Protein / Q000276:immunology; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D050296:Microbial Viability; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013290:Streptococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D050716:Complement C4b-Binding Protein; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D011994:Recombinant Proteins