Posted on 10/08/2001 5:06:14 PM PDT by Brian Kopp DPM
Chemical Neutralizes Anthrax Toxin
Nathan Seppa
Scientists have created a synthetic compound that disables the toxin that makes the bacterial disease anthrax so lethal. Meanwhile, another research team has discovered a gene that protects some mice against anthrax. These findings could lead to an antidote to the anthrax toxin and help clarify the mechanism by which it kills.
Whether the new compound can serve as an antitoxin in people remains unclear since the scientists have tested it only in rats, says R. John Collier of Harvard Medical School in Boston. Nevertheless, the concept of neutralizing anthrax toxin has appeal because the current treatments, which target the bacterium, and the vaccine now in use have drawbacks.
When a person inhales spores of Bacillus anthracis—the microbe that causes anthrax—they unleash three proteins that combine to form a toxin. This triad makes blood pressure plummet, causes hemorrhaging, and can lead to coma and death.
The proteins attack human cells as a team. One protein—protective antigen (PA)—binds to a receptor on the cell surface and is cleaved by enzymes there. The part of PA that remains stuck, called PA63, provides a docking site for the other anthrax proteins—lethal factor and edema factor. Once assembled, the toxin enables lethal factor to enter the cell. There, it chops up proteins, setting into motion the chain of events that leads to anthrax's symptoms, says Nicholas C. Duesbery of the Van Andel Research Institute in Grand Rapids, Mich.
Since no drug in use at present disables the toxin, Collier and his colleagues set out to create such a compound. First, they identified a peptide, or partial protein, that bonds to PA63 in lab tests. Next, they linked together multiple copies of the peptide. In test tubes, this synthetic molecule, which they call polyvalent inhibitor (PVI), prevented the natural anthrax proteins from binding to PA63.
When injected into rats, PVI protected the animals against subsequent exposure to 10 times the normally lethal dose of anthrax toxin, the researchers report in the October Nature Biotechnology. Without PVI treatment, rats died within hours.
Antibiotics can kill B. anthracis but have no effect on the toxin already present in the body when symptoms appear, says Robert C. Liddington of the Burnham Institute in La Jolla, Calif. The vaccine poses problems, too. It can cause side effects, and "it's hard to justify vaccinating a whole country against one particular agent of biological terrorism," he says.
Ideally, a toxin antidote would be mass-produced and kept in storage around the country, Collier says.
Researchers are currently charting the anthrax proteins' course in the body. In the Oct. 2 Current Biology, William F. Dietrich of the Howard Hughes Medical Institute and Harvard Medical School in Boston and his colleagues report that certain variations of a gene called Kif1C, which encodes a protein that ushers other proteins around inside cells, protect mice from the effects of the anthrax toxin.
"We've got the PA63 molecular activity on one end and the disease on the other end. The Kif1C gene gives us some clues as to where to look in between," Duesbery says.
References:
Mourez, M., ... and R.J. Collier. 2001. Designing a polyvalent inhibitor of anthrax toxin. Nature Biotechnology 19(October):958.
Watters, J.W., ... and W.F. Dietrich. 2001. Kif1C, a kinesin-like motor protein, mediates mouse machophage resistance to anthrax lethal factor. Current Biology 11(Oct. 2):1503.
Further Readings:
Dixon, T.C., et al. 1999. Anthrax. New England Journal of Medicine 341:815.
Duesbery, N.S., et al. 1998. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280:734.
Petosa, C., et al. 1997. Crystal structure of the anthrax toxin protective antigen. Nature 385:833.
Seppa, N. 2001. New anthrax treatment works in rats. Science News 159(May 12):296.
Travis, J. 2000. Viruses that slay bacteria draw new interest. Science News 157(June 3):358.
______. 1998. New clue hints at how anthrax kills. Science News 153(May 9):299.
Sources:
R. John Collier
Department of Microbiology and Molecular Genetics Harvard Medical School 200 Longwood Avenue Boston, MA 02115
William F. Dietrich
Department of Genetics Howard Hughes Medical Institute Harvard Medical School Boston, MA 02115
Nicholas S. Duesbury
Van Andel Research Institute 3333 Bostwick Avenue N.E. Grand Rapids, MI 49503
Robert C. Liddington
Burnham Institute 10910 North Torrey Pines Road La Jolla, CA 92037
From Science News, Vol. 160, No. 14, Oct. 6, 2001, p. 212.
Copyright ©2001 Science Service. All rights reserved. 1719 N St., NW, Washington, DC 20036 | 202-785-2255 | scinews@sciserv.org
I know I have a bad attitude, but things like this remind me of the cold war adage:
"In the event of nuclear attack, put your head between your knees, cover your ears, and kiss your $$$ goodbye."
Cipro can also cause bone problems in kids. And pregnant women can't take it, since the baby's bones are affected with all three.
Section II - Anthrax
Headquarters Departments of the Army, the Navy, and the Air Force, and Commandant, Marine Corps
Peer Review Status: Internally Peer Reviewed
2-9. Control of Patients, Contacts, and Treatment Areas
Report all cases to line and medical chains of command.
Employ Standard Precautions for handling, treating, and moving all active cases.
Use sporicidal agents, such as disinfectant strength iodophors, in MTFs for general area disinfection. Antiseptic strength iodophors are not sporicidal. Hypochlorite solutions may be attenuated by organic matter, but will provide a disinfectant capability when used in a 5-percent solution. The hypochlorite solution should be replaced frequently. Autoclaving, steam sterilizing, or burning is required for complete eradication of spores.
The real good news is that all the batch of Anthrax spores that were smuggled into the USA are all sensitive to PCN!
That's what's not being reported on the TV or here on FR.
Let's Roll,
DrMike
Shalom,
DrMike
Stay Safe !
I read recently that they don't know. But hey, they tried!
Not having taken the Doxycycline, I can't guarantee that it's good, but everything appears to be legit. Shipping has been ~3 weeks, and Credit Card billing has worked with no problems.
There's a $50 minimum, so maybe pick up some Amoxycillin too. That's safer for kids and pregnant women. No good for anthrax, but better for ear/nose/throat infections, and you never know what you'll need.
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