Multivalent bacterial inhibitor protects against toxins

Certain bacteria, such as enterohemorrhagic Escherichia coli O157:H7, are difficult to treat because destruction of the cells by standard antibiotics releases bacterial toxins. Pavel Kitov et al. have created a class of multivalent inhibitors that can bind and sequester such toxins through multiple, low-affinity interactions. The authors designed a polymer scaffold that aggregated the E. coli Shiga toxin and a circulating plasma protein, human serum amyloid P (HuSAP), which is a component of the innate immune system. Both the toxin and the immune protein bind their respective ligands—the Pktrisaccharide and cyclic pyruvate ketal, respectively— extremely weakly. The authors arranged these ligands precisely on the scaffold to achieve sufficient binding of the target toxins and neutralization of immune proteins. The inhibitor, termed (S)-PolyBAIT, protected mice expressing HuSAP from the effects of a toxic dose of the Shiga toxin, which causes hemolytic-uremic syndrome. (S)-PolyBAIT promoted the formation of stable toxin–HuSAP complexes and directed them for disposal in the reticuloendothelial system. This class of inhibitors, used in conjunction with standard antibiotics, could be an effective therapy for many types of bacteria that produce soluble toxins, the authors say. — F.A.