title: Analysis of the BadA stalk from Bartonella henselae reveals domain-specific and domain-overlapping functions in the host cell infection process.
abstract: Human pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck-stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analysed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head-bearing and headless deletion mutants with different lengths (containing one or four neck/stalk repeats in the neck-stalk module) were produced and functionally analysed for their ability to bind to fibronectin, collagen and endothelial cells and to induce VEGF secretion. Whereas a head-bearing short version (one neck/stalk element) of BadA lacks exclusively fibronectin binding, a substantially truncated headless BadA mutant was deficient for all of these biological functions. The expression of a longer headless BadA mutant (four neck/stalk repeats) restored fibronectin and collagen binding, adherence to host cells and the induction of VEGF secretion. Our data suggest that (i) the stalk of BadA is exclusively responsible for fibronectin binding and that (ii) both the head and stalk of BadA mediate adherence to collagen and host cells and the induction of VEGF secretion. This indicates overlapping functions of the BadA head and stalk.
authors: Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universitätsklinikum, Goethe-Universität, Paul Ehrlich Str.40, 60596 Frankfurt am Main, Germany.
authors: Patrick O
authors: PO
authors: Kaiser
authors: Dirk
authors: D
authors: Linke
authors: Heinz
authors: H
authors: Schwarz
authors: Jack C
authors: JC
authors: Leo
authors: Volkhard A J
authors: VA
authors: Kempf
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D018416:Bartonella henselae / Q000472:pathogenicity*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004252:DNA Mutational Analysis; D042783:Endothelial Cells / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017384:Sequence Deletion
chemical_list: D018829:Adhesins, Bacterial; D005353:Fibronectins; D050505:Mutant Proteins; D003094:Collagen