A team of European scientists working with Bartonella bacteria has identified a new mechanism of bacterial pathogenesis.
Bartonella bacterium (Ceshencam)
Bacteria that cause chronic infections have an amazing but yet poorly known ability to subvert immune response, live and produce offspring, enter and wake up from a dormant phase to cause, in some instances, deadly complications.
Bartonella bacteria cause chronic infections in mammals and are typically transmitted to new hosts mainly by fleas, lice and ticks, but also via direct tissue trauma (e.g. cat scratches).
One very notable feature of these bacteria is their ability to cause vasoproliferative tumors in patients suffering from immunodeficiency. If left untreated, these foci of inflammation maintain a chronic infection and contribute to transmitting bacteria to new hosts.
A study, published in the journal Proceedings of the National Academy of Sciences, demonstrates that Bartonella henselae injects a protein called BepA into vascular endothelial cells and that this protein manipulates cAMP-mediated cell signaling using a previously unknown mechanism.
BepA directly binds the host cell adenylyl cyclase, which is an enzyme responsible for the production of cAMP.
However, the binding of BepA to the adenylyl cyclase does not activate cAMP production per se, but the adenylyl cyclase rather becomes more sensitive to its natural activator, stimulatory G-protein (Gαs).
The cellular concentration of cAMP increases and prevents the death of the host cell. BepA significantly prolongs the lifespan of the host cell and partly contributes to the formation of vasoproliferative tumors.
Several bacterial species are known to manipulate host cell functions via cAMP-mediated cell signaling.
The symptoms are typically very strong and may even be deadly. The best-known example is Vibrio cholerae and its cholera toxin, which modifies Gαs into a permanently adenylyl cyclase-stimulating form. BepA, in turn, manipulates host cell signaling in a subtle sophisticated manner, which is ideal for chronic persistence of Bartonella henselae in the infected vascular endothelium.
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Bibliographic information: Pulliainen AT et al. 2012. Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production. PNAS June 12, 2012 vol. 109, no. 24, 9581-9586; doi: 10.1073/pnas.1117651109
