title: The fibrinogen receptor FbsA promotes adherence of Streptococcus agalactiae to human epithelial cells.
abstract: Streptococcus agalactiae is a major cause of bacterial pneumonia, sepsis, and meningitis in human neonates. During the course of infection, S. agalactiae adheres to a variety of epithelial cells but the underlying mechanisms are only poorly understood. The present report demonstrates the importance of the fibrinogen receptor FbsA for the streptococcal adherence and invasion of epithelial cells. Deletion of the fbsA gene in various S. agalactiae strains substantially reduced their binding of soluble fibrinogen and their adherence to and invasion of epithelial cells, indicating a role of FbsA in these different processes. The adherence and invasiveness of an fbsA deletion mutant were partially restored by reintroducing the fbsA gene on an expression vector. Heterologous expression of fbsA in Lactococcus lactis enabled this bacterium to adhere to but not to invade epithelial cells, suggesting that FbsA is a streptococcal adhesin. Flow cytometry experiments revealed a dose-dependent binding of FbsA to the surface of epithelial cells. Furthermore, tissue culture experiments exhibited an intimate contact of FbsA-coated latex beads with the surfaces of human epithelial cells. Finally, host cell adherence and invasion were significantly blocked in competition experiments with either purified FbsA protein or a monoclonal antibody directed against the fibrinogen-binding epitope of FbsA. Taken together, our studies demonstrate that FbsA promotes the adherence of S. agalactiae to epithelial cells but that FbsA does not mediate the bacterial invasion into host cells. Our results also indicate that fibrinogen-binding epitopes within FbsA are involved in the adherence of S. agalactiae to epithelial cells.
authors.affiliation: Department of Microbiology and Biotechnology, University of Ulm, Albert-Einstein-Allee 11, D-89069, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schubert
authors.forename: Katherina
authors.initials: K
authors.lastname: Zakikhany
authors.forename: Giampiero
authors.initials: G
authors.lastname: Pietrocola
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinke
authors.forename: Pietro
authors.initials: P
authors.lastname: Speziale
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eikmanns
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Reinscheid
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008855:Microscopy, Electron, Scanning; D039341:Receptors, Fibrinogen / Q000235:genetics / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D039341:Receptors, Fibrinogen; D005340:Fibrinogen