Elucidating the in Vivo Targets of Bacterial Toxins

Many bacterial pathogens release soluble proteins, referred to as toxins, which damage host cells during disease. In the past, bacterial toxins have been studied extensively using cultured cells, and in vitro biochemical systems. However, little is known about the types of cells targeted by toxins during the disease process while within the host. This has limited our understanding of these important virulence factors. To address this problem, we have recently used transparent zebrafish embryos to follow toxin activity in a multiorgan system in real-time. Zebrafish provide many advantages over more traditional animal models, since major organs can be directly visualized by light microscopy. This allows one to follow toxin activity and organ damage as it occurs following intoxication. As proof-of-principle, we have recently exploited the zebrafish embryo to identify the activities of Clostridium difficile toxin B, an intracellular bacterial toxin. By using the zebrafish system we have been able to identify a major organ, the heart, targeted by this toxin.