Shiga Toxin Inhibitor Could Help Combat Food Poisoning

Using a polymer as a framework for delivering multiple copies of an agent that binds a Shiga toxin produced by the food-borne pathogen Escherichia coli O157:H7, researchers have been able to enhance the agent's toxin-clearing power (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0804919105). David R. Bundle of the University of Alberta and coworkers previously showed that a heterobifunctional ligand called BAIT, in which one ligand that binds Shiga toxin is linked to another ligand that binds an immune protein, induces formation of a toxin/immune protein complex. The toxin and protein both have pentameric structures and are held together by five BAIT molecules. But the BAIT ligand has a short circulation lifetime and does not work in animals. In their latest research, Bundle and coworkers find that polyBAIT—heterobifunctional ligands preorganized on a polymer—is about 1,000 times more potent than BAIT at forming toxin/immune protein complexes. When polyBAIT is injected into mice that have been given a lethal dose of Shiga toxin, the immune protein clears the toxin to the liver and all the mice survive. The researchers believe this approach may also be useful for directing therapeutic proteins to membrane receptors.