title: The head of Bartonella adhesin A is crucial for host cell interaction of Bartonella henselae.
abstract: Human pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders (e.g. bacillary angiomatosis). Expression of Bartonella adhesin A (BadA) is crucial for bacterial autoagglutination, adhesion to host cells, binding to extracellular matrix proteins and proangiogenic reprogramming via activation of hypoxia inducible factor (HIF)-1. Like the prototypic Yersinia adhesin A, BadA belongs to the class of trimeric autotransporter adhesins and is constructed modularly consisting of a head, a long and repetitive neck-stalk module and a membrane anchor. Until now, the exact biological role of these domains is not known. Here, we analysed the function of the BadA head by truncating the repetitive neck-stalk module of BadA (B. henselae badA(-)/pHN23). Like B. henselae Marseille wild type, B. henselae badA(-)/pHN23 showed autoagglutination, adhesion to collagen and endothelial cells and activation of HIF-1 in host cells. Remarkably, B. henselae badA(-)/pHN23 did not bind to fibronectin (Fn) suggesting a crucial role of the deleted stalk domain in Fn binding. Additionally, the recombinantly expressed BadA head adhered to human umbilical vein endothelial cells and to a lesser degree to epithelial (HeLa 229) cells. Our data suggest that the head represents the major functional domain of BadA responsible for host adhesion and angiogenic reprogramming.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, Eberhard-Karls-Universität, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Kaiser
authors.forename: Tanja
authors.initials: T
authors.lastname: Riess
authors.forename: Carola L
authors.initials: CL
authors.lastname: Wagner
authors.forename: Dirk
authors.initials: D
authors.lastname: Linke
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
authors.forename: Heinz
authors.initials: H
authors.lastname: Schwarz
authors.forename: Günter
authors.initials: G
authors.lastname: Raddatz
authors.forename: Andrea
authors.initials: A
authors.lastname: Schäfer
authors.forename: Volkhard A J
authors.initials: VA
authors.lastname: Kempf
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016917:Angiomatosis, Bacillary / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D018416:Bartonella henselae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002415:Cats; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011993:Recombinant Fusion Proteins