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article imageScientists find a way to block botulism poisoning

By Tim Sandle     Jul 20, 2014 in Science
Scientists have discovered how bacterial toxins that cause food-borne botulism are absorbed through the intestinal lining and into the bloodstream. The study offers insight into developing new approaches for blocking this poisonous substance.
Botulism is a rare and often fatal paralytic illness due to a neurotoxin produced by Clostridium botulinum bacteria, which can appear in rotted, uncooked foods and in soil. Listed as a Tier 1 agent by the Centers for Disease Control & Prevention, the botulinum toxin is also a potential biological weapon.
Using a crystal structure of a complex protein compound of botulinum neurotoxin, UCI News reports how researchers have found that these compounds – called clostridial hemagglutinin (HA) – bind with epithelial cell proteins in the intestines of patients, initiating a process that disrupts the close intercellular seals, enabling the complex toxin molecules to slip through the epithelial barrier.
By identifying this novel process by which the toxin compound manages to, in a sense, open the door from inside, scientists can better understand how to seek new methods to prevent these deadly toxins from entering the bloodstream.
In further tests the research group designed a mutated version of the botulism compound, based on the novel crystal structure, in which HA would not bind with the epithelial cell protein E-cadherin. Even though this lab-made toxin compound contains the fully active live toxin molecule, it was not orally toxic when tested on mice because the mutated HA cannot break up the intercellular seals and, therefore, the toxin compound cannot be absorbed through the epithelial layer.
The researchers are hopeful that this could lead to the identification of small molecules able to stop HA from binding with epithelial cell proteins, thus preventing the toxin invasion.
The study has been reported to the journal PLOS Pathogens. The study is titled "Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity."
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