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Bartonella adhesin a mediates a proangiogenic host cell response
Tanja Riess1, Siv G E Andersson, Andrei Lupas
1Institut für Medizinische Mikrobiologie und Hygiene, Eberhard-Karls-Universität, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
The Journal of Experimental Medicine
|November 10, 2004
Summary
Bartonella henselae adhesin A (BadA) is a large bacterial protein that helps the bacteria bind to host cells and prevents phagocytosis. BadA is a key factor in Bartonella henselae infections and may cause vasculoproliferative disorders.
Area of Science:
- Microbiology
- Pathogen-host interactions
- Bacterial pathogenesis
Background:
- Bartonella henselae is a bacterium known to cause vasculoproliferative disorders in humans.
- The mechanisms by which B. henselae establishes infection and causes disease are not fully understood.
- Identifying bacterial factors involved in pathogenesis is crucial for understanding and treating these infections.
Purpose of the Study:
- To identify and characterize novel adhesins of Bartonella henselae.
- To investigate the role of Bartonella adhesin A (BadA) in bacterial binding, host cell interaction, and virulence.
- To explore the potential involvement of BadA in the development of vasculoproliferative disorders.
Main Methods:
- Identification and molecular characterization of the Bartonella adhesin A (BadA) gene and protein.
- Complementation of a BadA-deficient mutant to restore protein expression.
- In vitro assays to assess bacterial binding to extracellular matrix proteins and endothelial cells.
- Analysis of host cell responses, including hypoxia-inducible factor 1 activation and cytokine secretion.
- Immunological assessment of BadA expression in infected patients and animal models.
Main Results:
- A novel nonfimbrial adhesin, Bartonella adhesin A (BadA), a 340-kD outer membrane protein, was identified in B. henselae.
- BadA mediates the binding of B. henselae to extracellular matrix proteins and endothelial cells, potentially via beta1 integrins.
- BadA inhibits phagocytosis of B. henselae by host cells.
- Expression of BadA is essential for B. henselae-induced activation of hypoxia-inducible factor 1 and secretion of proangiogenic cytokines like vascular endothelial growth factor.
- BadA is immunodominant during B. henselae infections in humans and rodents.
Conclusions:
- Bartonella adhesin A (BadA) is a major virulence factor of B. henselae.
- BadA plays a critical role in bacterial adhesion, immune evasion, and host cell manipulation.
- BadA may contribute significantly to the induction of vasculoproliferative disorders associated with B. henselae infections.