Anthrax Research Today is a free monthly online journal that collates and summarizes the latest research about Anthrax, including details on bacillus anthracis, contagiousness, exposure, effects.

Chemical genetic screening identifies critical pathways in anthrax lethal toxin-induced pathogenesis.

Panchal RG, Ruthel G, Brittingham KC, Lane D, Kenny TA, Gussio R, Lazo JS, Bavari S

Target Structure-Based Drug Discovery Group, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.

Anthrax lethal toxin (LT)-induced cell death via mitogen-activated protein kinase kinase (MAPKK) cleavage remains questionable. Here, a chemical genetics approach was used to investigate what pathways mediate LT-induced cell death. Several small molecules were found to protect macrophages from anthrax LT cytotoxicity and MAPKK from cleavage by lethal factor (LF), without inhibiting LF enzymatic activity or cellular proteasome activity. Interestingly, the compounds activated MAPK-signaling molecules, induced proinflammatory cytokine production, and inhibited LT-induced macrophage apoptosis in a concentration-dependent manner. We propose that induction of antiapoptotic responses by MAPK-dependent or -independent pathways and activation of host innate responses may protect macrophages from anthrax LT-induced cell death. Altering host responses through a chemical genetics approach can help identify critical cellular pathways involved in the pathogenesis of anthrax and can be exploited to further explore host-pathogen interactions.

Published 23 March 2007 in Chem Biol, 14(3): 245-55.
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