CHOLERA TURN-ON

Abstract

AN IMPORTANT TOXIN behind cholera’s lethality activates itself by clamping down on a signaling molecule found only in hosts susceptible to the disease, a new study shows. This newly discovered triggering process may be common to multiple bacteria that cause food- and waterborne illnesses. The bacterium that causes cholera, a diarrheal illness that can be deadly, contains RTX, which stands for repeats in toxin, a protein that is thought to enhance the severity of the disease. RTX is nontoxic until its protease function is activated upon entering the host. Investigators have known that inositol hexakisphosphate (IP 6 ), a signaling molecule not found in bacteria but abundant in disease hosts, triggers RTX activation, but the activation mechanism has remained unclear. Now, a Stanford University team led by biochemist Matthew Bogyo and structural biologist K. Christopher Garcia suggests that IP 6 regulates RTX by triggering a structural rearrangement in its protease ( Science 2008, 322 , 265). The team’s X-ra...