Adherence to and invasion of human brain microvascular endothelial cells are promoted by fibrinogen-binding protein FbsA of Streptococcus agalactiae.
Streptococcus agalactiae is a frequent cause of bacterial sepsis and meningitis in neonates. During the course of infection, S. agalactiae colonizes and invades a number of host compartments, thereby interacting with different host tissues. Deletion of the fbsA gene, encoding the fibrinogen protein FbsA, significantly impaired the adherence and invasion of human brain microvascular endothelial cells (HBMEC) by S. agalactiae. The adherence and invasiveness of an fbsA deletion mutant were 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 HBMEC, suggesting that FbsA is a streptococcal adhesin. Finally, host cell adherence and invasion were significantly blocked in competition experiments with either purified FbsA fusion protein or a monoclonal antibody directed against the fibrinogen-binding epitope of FbsA. The S. agalactiae fbsA mutant induced a release of the neutrophil chemoattractant interleukin-8 (IL-8) equal to that induced by the wild type. Taken together, our studies demonstrate that FbsA promotes the adherence of S. agalactiae to HBMEC but that FbsA neither mediates the bacterial invasion into host cells nor plays a role in IL-8 release for HBMEC.
Pädiatrische Infektiologie, Klinik für Allgemeine Pädiatrie, Heinrich Heine Universität Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
Tobias
T
Tenenbaum
Christiane
C
Bloier
Rüdiger
R
Adam
Dieter J
DJ
Reinscheid
Horst
H
Schroten
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000382:microbiology*; D002352:Carrier Proteins / Q000502:physiology*; D042783:Endothelial Cells / Q000382:microbiology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000472:pathogenicity*
D001426:Bacterial Proteins; D002352:Carrier Proteins; C499709:FbsA protein, Streptococcus agalactiae; D016209:Interleukin-8