Scientists have identified a new mechanism1 of bacterial2 pathogenesis(发病原理) . The results of the research project, partly funded by the Academy of Finland, have been published in the journal Proceedings3 of the National Academy of Sciences of the United States of America (PNAS). Bacteria that cause chronic4 infections have an amazing but yet poorly known ability to subvert5(颠覆,推翻) immune response, live and produce offspring, enter and wake up from a dormant6(休眠的) phase to cause, in some instances, deadly complications.
Bartonella bacteria cause chronic infections in mammals (incl. humans), and are typically transmitted to new hosts mainly by arthropod vectors such as fleas7, lice and ticks, but also via direct tissue trauma8 (e.g. cat scratches).
One very notable feature of these bacteria is their ability to cause vasoproliferative tumours9 that resemble Kaposi's sarcoma in patients suffering from immunodeficiency (e.g. AIDS, aggressive cancer treatments, organ transplantation). If left untreated, these foci of inflammation maintain a chronic infection and contribute to transmitting bacteria to new hosts.
In his research, biologist Arto Pulliainen (University of Turku) has demonstrated that Bartonella henselae injects a protein called BepA into vascular10 endothelial cells and that this protein manipulates cAMP-mediated cell signalling using a previously11 unknown mechanism.
BepA directly binds12 the host cell adenylyl cyclase, which is an enzyme13 responsible for the production of cAMP. However, the binding14 of BepA to the adenylyl(腺苷) cyclase does not activate15 cAMP production per se, but the adenylyl cyclase rather becomes more sensitive to its natural activator16, stimulatory17 G-protein (Gαs). The cellular18 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 tumours.
Several bacterial species are known to manipulate host cell functions via cAMP-mediated cell signalling. The symptoms are typically very strong and may even be deadly. The best-known example is Vibrio cholerae and its cholera19 toxin20, which modifies Gαs into a permanently21 adenylyl cyclase-stimulating form. BepA, in turn, manipulates host cell signalling in a subtle sophisticated manner, which is ideal for chronic persistence22 of Bartonella henselae in the infected vascular(血管的) endothelium(内皮) .
The research has been carried out at the Universities of Basel and Turku.