A new mechanism for bacterial pathogenesis
Here is an interesting publication brought to my attention by Tabitha Harris (Summer session Micro) via Science Daily, and published recently in The Proceedings of the National Academy of Sciences. Bartonella infections occur in humans, and are typically transmitted by arthropod vectors, or perhaps more widely known by cat scratches. Astute watchers of House will immediately recall Bartonella infection as the agent in this episode from Season 7, where it was revealed that an insect vector was responsible.
Bartonella leads frequently to a chronic infection, and one sign that can result are tumor-like masses that significantly resemble the Kaposi’s Sarcoma found in HIV patients. These lesions contain viable bacteria which can act as reservoirs for transmission to new hosts. This is actually a fascinating pathogenesis mechanism for bacteria, as most exotoxins lead to disease damage by cellular destruction, not by proliferation of host cells. The organism is related to Rickettsia, however unlike the Rickettsias which lack peptidoglycan and reproduce as obligate intracellular parasites in a method not dissimilar to viruses, Bartonella can reproduce in cell-free medium.
Researchers at the University of Basel (Switzerland) and the University of Turku (Finland) have examined some of the molecular events of Bartonella infection. What Bartonella appears to do is to introduce an exotoxin called BepA into infected cells. BepA interacts with cellular signalling pathways mediated by adenyl cyclase, a key regulator of the eukaryotic cell cycle. The causative agent of cholera Vibrio cholerae also stimulates adenyl cyclase, and has a very profound effect on intestinal epithelial cells, which in turn produces extreme dysfunction in the ability of the intestines to resorb water. With Bartonella, the effect is much more subtle, and is specific for the endothelial cells which line vascular tissue. Inflammation is triggered by the infection, and BepA exotoxin promotes the endothelial cells to begin to divide, producing the tumor like mass.
The authors propose that this molecular hijacking of the cellular proliferation machinery (normally a phenomenon associated exclusively with the development of cancer cells) helps to explain how Bartonella is able to persist in chronic infections. There are examples of infectious agents which are able to promote cancer-like growths in the body; Human Papilloma Virus is one obvious example. However, the induction of cancer by a virus such as HPV requires the introduction of viral oncogenes (or cancer-promoting DNA sequences) into host cells in order for the cancer to develop. In the case of this bacterial infection, it is the introduction of an exotoxin into cells that promotes the formation of the mass. Consequently, once the bacteria have been eliminated by appropriate use of antibiotics, the mass has no metastatic potential because the genomes of those cells have not been altered. Since the proliferative cells are ones that normally will turn over in the human body, the mass will disappear when new normal cells replace the exotoxin damaged ones.
Posted on June 30, 2012, in Microbes in the News, Strange but True and tagged Bartonella, Proceedings of the National Academy of Sciences of the United States of America, Science Daily. Bookmark the permalink. Comments Off.