Antibiotic treatment may fail to protect individuals, if not started early 
enough, after infection with Bacillus anthracis, due to the continuing activity 
of toxins that the bacterium produces. Stable and easily stored inhibitors of 
the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event 
of an outbreak, due to natural causes or a bioweapon attack. The toxin's basic 
activity is to convert ATP to cAMP, and it is thus in principle a simple 
phosphatase, which means that many mammalian enzymes, including intracellular 
adenylcyclases, may have a similar activity. While nucleotide based inhibitors, 
similar to its natural substrate, ATP, were identified early, these compounds 
had low activity and specificity for EF. We used a combined structural and 
computational approach to choose small organic molecules in large, web-based 
compound libraries that would, based on docking scores, bind to residues within 
the substrate binding pocket of EF. A family of fluorenone-based inhibitors was 
identified that inhibited the release of cAMP from cells treated with EF. The 
lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic 
E. coli (ETEC) in a murine model, perhaps by serving as a quorum sensor. These 
inhibitors are now being tested for their ability to inhibit Anthrax infection 
in animal models and may have use against other pathogens that produce toxins 
similar to EF, such as Bordetella pertussis or Vibrio cholera.