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Abstract:
The humanpathogenic bacterium Bartonella henselae causes 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. BadA belongs to the class of the lollipop-like structured trimeric autotransporter adhesins (TAAs) and is modularly constructed consisting out of a head, a long and repetitive neck- stalk module and a membrane anchor. Until now, the exact biological roles of these domains in the infection process remains unknown. Here, we analyzed the functions of certain BadA domains in greater detail. For this purpose, deletion mutants were produced by truncating the repetitive neck- stalk module and deleting different head subdomains of BadA. Like wildtype bacteria, a mutant with a nearly completely truncated stalk exhibited autoagglutination, adhesion to collagens and endothelial cells (ECs) and induced the secretion of proangiogenic cytokines (VEGF). Remarkably, B. henselae expressing only parts of the stalk bound fibronectin. Deletions of several head subdomains revealed no specific attribution of domain-function relationships. Our data revealed that the fibronectin binding ability of the BadA is located in the stalk domain. The adhesion to collagen and ECs and the secretion of proangiogenic cytokines is mediated by the neck-stalk module and by the single subdomains of the BadA head. These findings suggest overlapping functions of certain BadA domains in the infection process of the host.
