Bartonella adhesin a mediates a proangiogenic host cell response.
Bartonella henselae causes vasculoproliferative disorders in humans. We identified a nonfimbrial adhesin of B. henselae designated as Bartonella adhesin A (BadA). BadA is a 340-kD outer membrane protein encoded by the 9.3-kb badA gene. It has a modular structure and contains domains homologous to the Yersinia enterocolitica nonfimbrial adhesin (Yersinia adhesin A). Expression of BadA was restored in a BadA-deficient transposon mutant by complementation in trans. BadA mediates the binding of B. henselae to extracellular matrix proteins and to endothelial cells, possibly via beta1 integrins, but prevents phagocytosis. Expression of BadA is crucial for activation of hypoxia-inducible factor 1 in host cells by B. henselae and secretion of proangiogenic cytokines (e.g., vascular endothelial growth factor). BadA is immunodominant in B. henselae-infected patients and rodents, indicating that it is expressed during Bartonella infections. Our results suggest that BadA, the largest characterized bacterial protein thus far, is a major pathogenicity factor of B. henselae with a potential role in the induction of vasculoproliferative disorders.
Riess
Tanja
T
Institut für Medizinische Mikrobiologie und Hygiene, Eberhard-Karls-Universität, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
Andersson
Siv G E
SG
Lupas
Andrei
A
Schaller
Martin
M
Schäfer
Andrea
A
Kyme
Pierre
P
Martin
Jörg
J
Wälzlein
Joo-Hee
JH
Ehehalt
Urs
U
Lindroos
Hillevi
H
Schirle
Markus
M
Nordheim
Alfred
A
Autenrieth
Ingo B
IB
Kempf
Volkhard A J
VA
D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D000818:Animals; D018416:Bartonella henselae / Q000378:metabolism* / Q000648:ultrastructure; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D042783:Endothelial Cells / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D018829:Adhesins, Bacterial; D043924:Angiogenesis Modulating Agents; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins