Researchers locate anthrax's Achilles' heal
Bacteria a master at using siderophores to extract iron from human hosts; researchers identify stealth protein that ovecomes human defenses; discovery could lead to improved drugs and testing
While federal investigators continue the hunt for 2001’s anthrax-wielding terrorist, chemists at the University of California at Berkeley, the University of Mississippi Medical Center in Jackson and the Fred Hutchinson Cancer Research Center in Seattle may have located the bacteria’s Achilles’ heel. The scientists uncovered the trick while studying how anthrax steals iron from human hosts to grow and reproduce. Many bacteria (including the benign Escherichia coli that populate the human stomach) take advantage of their human hosts’ iron stores, and this process has recently become a major area of interest to researchers working on anthrax and other infectious pathogens
Anthrax bacteria are known to produce two small molecules — bacillibactin and petrobactin — that snatch iron away from the human body’s iron transporter molecules, known as transferrin. These scavengers, or “siderophores,” are essential to anthrax’s ability to grow rapidly, especially after the spores are inhaled, though why the bacteria need two siderophores to do the job has long been an enigma.
Not anymore. According to the researchers, anthrax bacteria require two siderophores working by two different mechanisms. Siderocalin, the human immune protein, defensively binds bacillibactin and effectively sidelines it, the researchers found. To get around this, anthrax developed a second iron scavenger, petrobactin, which is not bound by siderocalin. The researchers believe that, although the human immune system has not yet developed a natural counterattack to this second siderophore, it might be possible to create one artificially as a treatment for infection. Possible appliactions include: anti-anthrax drugs that target petrobactin synthesis or iron-uptake, or anthrax sensors that detect petrobactin, which is not known to occur in any other pathogenic bacteria.
A paper based on these findings can be found in the 5 December issue of the Proceedings of the National Academy of Sciences.
-read more in this university news release
