title: Bartonella adhesin a mediates a proangiogenic host cell response.
abstract: 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.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Eberhard-Karls-Universität, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Riess
authors.forename: Siv G E
authors.initials: SG
authors.lastname: Andersson
authors.forename: Andrei
authors.initials: A
authors.lastname: Lupas
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Andrea
authors.initials: A
authors.lastname: Schäfer
authors.forename: Pierre
authors.initials: P
authors.lastname: Kyme
authors.forename: Jörg
authors.initials: J
authors.lastname: Martin
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Wälzlein
authors.forename: Urs
authors.initials: U
authors.lastname: Ehehalt
authors.forename: Hillevi
authors.initials: H
authors.lastname: Lindroos
authors.forename: Markus
authors.initials: M
authors.lastname: Schirle
authors.forename: Alfred
authors.initials: A
authors.lastname: Nordheim
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.forename: Volkhard A J
authors.initials: VA
authors.lastname: Kempf
mesh_terms: 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
chemical_list: D018829:Adhesins, Bacterial; D043924:Angiogenesis Modulating Agents; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins