Noxious intestinal bacteria can latch onto a sticky glycoprotein called CEACAM6. Now, Carvalho et al. reveal that this cell adhesion molecule enables the bugs to colonize the intestinal lining and cue the symptoms of Crohn's disease in mice.
An abnormal immune response to intestinal microbes is thought to cause the inflammation and tissue damage of Crohn's disease. Whether immune cells turn against harmless bacteria or whether the bacterial balance in the intestine is out of whack is still a matter of dispute. This group had previously discovered that Crohn's disease patients harbor excess amounts of CEACAM6 in the ileum of the small intestine. They also showed that pathogenic E. coli binds to CEACAM6 in vitro.
To confirm that the bacteria–CEACAM6 interaction promotes inflammation and disease, the team tested transgenic mice carrying a bacterial artificial chromosome that included the gene for human CEACAM6. Feeding the transgenic animals adherent-invasive E. coli (AIEC), which is common in Crohn's disease patients, spurred severe intestinal inflammation and erosion that killed 80% of the animals within a week. Control mice lacking the inserted genes rapidly eliminated the bug and remained healthy.
Extensions on the bacteria, called type 1 pili, enabled bacteria to adhere to CAECAM6 on intestinal surfaces. AIEC lacking these structures were unable to colonize either control mice or animals carrying human CEACAM6. Thus, Crohn's disease patients might benefit from a vaccine or treatment that prevents type 1 pili from getting a grip on CEACAM6. Such an inhibitor might not harm the bacteria directly and thus could have another plus—it wouldn't be likely to provoke drug resistance in the bacteria.