In the online edition of the Proceedings of the National Academy of Sciences, a team led by Wei-Jen Tang of the University of Chicago shows that in vitro adefovir dipivoxil (sold as Hepsera) can effectively reduce the effects of edema factor, one of the two deadly toxins produced by anthrax.
"These toxins pack a one-two punch that makes inhalational anthrax extremely harmful," said Tang, an associate professor in the Ben May Institute for Cancer Research at the University of Chicago. "For the first time, we have a clinically approved drug that, at least in tissue culture, completely eradicates half of that toxic team, and does it at non-toxic doses."
Until the fall of 2001, Bacillus anthracis, the bacterium that causes anthrax, was considered an obscure agricultural pathogen with a few interesting properties. But that September and October someone began sending threatening letters stuffed with anthrax spores to several politicians and journalists.
Nearly half (5/11) of those infected by breathing in the spores died from the disease. Many of those who survived have ongoing symptoms such as fatigue, shortness of breath and memory loss. "This highlights an urgent need," note the authors, "for a more effective treatment."
The anthrax mailings triggered a run on antibiotics used to treat infection. But these drugs only work in the early stages of anthrax infection, before the bacteria have had time to spread and secrete toxins, which are not affected by antibiotics.
These toxins, edema factor and lethal factor -- as well as a molecular escort called protective antigen that helps the toxins enter cells -- are what makes this microbe so deadly.
In the early stages of an infection, edema factor interferes with the host's immune response, allowing t
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
16-Feb-2004