Typhoid toxin’s deadly design

Typhoid fever, one of the longest-known diseases in human history, still claims more than 200,000 lives a year globally. But the molecular factors that make Salmonella Typhi far more virulent than closely related Salmonella bacteria that cause the temporary abdominal distress associated with food poisoning have been a mystery.

A Yale study has now revealed how S. Typhi packs its lethal punch, a discovery that could lead to the development of effective vaccines and other new therapies against typhoid fever.

Nearly a decade ago, a research team led by Jorge Galán, Ph.D., D.V.M., chair and Lucille P. Markey Professor of Microbial Pathogenesis, identified a toxin unique to S. Typhi. In follow-up work published in the July 11 issue of Nature, Galán and colleagues report that delivering the toxin alone to mice produced the main symptoms of typhoid fever. The team also solved the atomic structure of the toxin and identified the cellular receptors that guide the toxin to its site of action.

“What makes this so exciting for us is that vaccines and therapeutics that target toxins have an excellent track record of success” in diseases such as tetanus and botulism, says Galán, whose lab has begun a search for new typhoid fever treatments.