“Beads on a String” Represents Novel Approach for Neutralizing Toxins

Researchers at Cummings School of Veterinary Medicine at Tufts University have unveiled a novel strategy for neutralizing (pathogens) unwanted molecules and clearing them from the body.

The strategy utilizes chains of binding agents, like beads on a string, which target two sites on one or more pathogenic molecules to neutralize their activity and promote their clearance by the body’s immune system. This low-cost, easy-to-replicate tool has demonstrated applications against several different toxins, from those found in contaminated food to those used in bioterrorism. This strategy may also prove effective in targeting other types of pathogens.

The research team, led by Charles B. Shoemaker, Ph.D., professor of biomedical sciences at Tufts University’s Cummings School of Veterinary Medicine, demonstrated the method’s efficacy in preventing the symptoms of botulism, a rare but deadly disease caused by Clostridium botulinum neurotoxin (BoNT), considered one of the most dangerous bioterror threat agents. The findings were presented last year in PLoS ONE.

Currently, antitoxins are difficult to produce and have a short shelf life, making them very expensive. This new approach provides a low-cost way to develop highly effective antitoxins.

This method has the potential to target a number of pathogens – not only toxins such as BoNT, but viruses or inflammatory cytokines. It is an important platform through which to address other significant diseases, says Saul Tzipori, BVSc., DSc, PhD, professor of biomedical sciences and director of the Division of Infectious Diseases at the Cummings School.

Shoemaker and his team had earlier found that pools of small ‘tagged’ binding agents were highly effective in targeting toxins, neutralizing their function, and flagging them for removal via the body’s immune system in the presence of an anti-tag monoclonal antibody.

The group has now successfully taken the research further by building longer strings of binding agents that target multiple toxins with a single molecule—for example, the two types of Shiga toxins that are produced by some E. coli found in contaminated foods or the two toxins produced by hospital-acquired C. difficile infections. Linking binding agents together also leads to much more potent neutralization of the targeted toxin(s) or pathogen(s).

According to Shoemaker, a major advantage of this beads on a string approach is that, unlike treatments that only neutralize toxins, this treatment both neutralizes toxins and ensures their rapid clearance from the body. Agents that only neutralize their pathogenic target will eventually dissociate which will allow the pathogen to continue doing damage if it is not eliminated, he said.