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Key Anthrax Virulence Factor Discovered
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"Bacteria produce nitric oxide immediately upon germination, in the first two hours of infection," he explained. "Macrophages produce their own much later, 12 hours post-infection. So, the bacteria takes advantage of its own nitric oxide, as a preemptive strike to protect itself against future nitric oxide attack."
Indeed, he noted that during spore formation, anthrax pathogens store some bNOS, so it will be available immediately upon germination, when the bacteria are most vulnerable.
Bacterial "spores" are seed-like structures the bacteria form to protect themselves against unfavorable environmental conditions. Inhalation of anthrax spores (as occurred within the U.S. Postal Service in late 2001) is especially dangerous, as the spores are engulfed by macrophages, inside which they germinate and escape to spread the infection.
Now Nudler and his team are searching for small molecule inhibitors that can selectively target bNOS while leaving its human counterpart enzyme alone.
Given the differences between the two proteins, he said, "There is a great chance we can find a specific molecule that can inhibit it."
Another potential biothreat breakthrough was also published in the same issue ofPNAS. Yoshihiro Kawaoka, of the University of Wisconsin, Madison, and colleagues described a new, potentially safer way to grow ebola virus in culture -- an advance that could enable researchers to handle the pathogen in less-restrictive facilities and thus facilitate wider research into both its life cycle and the development of antiviral therapeutics.
More information
For more on anthrax, visit the U.S. Centers for Disease Control and Prevention.
SOURCES: Evgeny Nudler, Ph.D., professor, biochemistry, New York University School of Medicine, New York City; Philip Tierno Jr., director, clinical microbiology & immunology, Departments of Microbiology & Pathology, New York University Medical Center, New York City; Jan. 22-25, 2008,Proceedings of the National Academy of Sciences



