Scientists at the Yale University School of Medicine have proposed an explanation for how Salmonella Typhi, the bacterium that causes typhoid fever, kills 200 thousands people every year.

Typhoid fever is one of the oldest documented diseases known to have afflicted mankind but what makes it so lethal has remained a mystery for centuries. This disease is believed to have killed Athenian leader Pericles and a third of the population of the Greek city in 430 BC during the Peloponnesian War and has perplexed doctors ever since.

Untreated, typhoid fever kills up to 20 percent of those it infects, however many of those who survive remain carriers for life but show no symptoms. This fact explains why fever, illness and death followed from job to job the notorious carrier Mary Mallon, best known as Typhoid Mary. A cook for wealthy New England families, she is believed to have unwittingly infected several dozen people in the early 20th century.

Although the cause of typhoid fever has been known for over a century, what makes Salmonella Typhi so deadly has remained a mystery.

Now, Yale scientists have shown that the answer to this mystery may be typhoid toxin. They for the first time describe the structure of the toxin, created from the merger of two separate and powerful toxins, and show that it causes disease in mice.

The toxin helps explain why typhoid fever has such different symptoms than an infection by its close genetic cousin Salmonella, the common cause of food poisoning.

The atomic structure of the toxin and its receptor described in a paper published in the journal Nature, may pave the way to new life-saving therapeutics.

“What makes this so exciting for us is that vaccines and therapeutics that target toxins have an excellent track record of success,” said study senior author Prof Jorge Galan.

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Bibliographic information: Jeongmin Song et al. Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin. Nature, published online July 10, 2013; doi:10.1038/nature12377