- SAN DIEGO---BCTP looks like skim milk. Laboratory rats gain weight when
they eat it. Spray it on your lawn and the grass will thrive. But according
to tests conducted by University of Michigan scientists, this seemingly
benign material could be a potent weapon against anthrax---one of the deadliest
bacteria on Earth.
-
- In a presentation at the Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) on Sept. 26,
Michael Hayes, research associate in the U-M Medical School, presented
experimental evidence of BCTP's ability to destroy anthrax spores both
in a culture dish and in mice exposed to anthrax through a skin incision.
James R. Baker Jr., M.D., professor of internal medicine and director of
the Center for Biologic Nanotechnology in the U-M Medical School, directed
the research study.
-
- BCTP was developed by D. Craig Wright,
M.D., chief research scientist at Novavax, Inc.---a bio-pharmaceutical
company in Columbia, Md.---and president of Novavax Biologics Division.
According to Wright, the material is made of water, soybean oil, Triton
X 100 detergent and the solvent tri-n-butyl phosphate.
-
- "One of the most remarkable characteristics
of this material is its ability to rapidly destroy a wide variety of dangerous
bacteria and viruses, while remaining non-toxic to people, animals or the
environment," Baker said.
-
- BCTP's effectiveness against anthrax
spores is especially significant, because they are so difficult to kill.
"Spores are like freeze-dried bacteria," Baker explained. "Their
tough outer coat is resistant to disinfectants, freezing, drought, virtually
anything we can throw at them. Spores can survive in the environment for
many years and still generate live bacteria when given the right combination
of water, nutrients and temperature."
-
- Concentrated doses of strong disinfectants
like bleach or formaldehyde will kill anthrax spores, according to Baker.
Unfortunately, they also are toxic to people and the environment, which
makes them useless for decontaminating a person, a piece of land or equipment
exposed to the bacteria.
-
- Since the Persian Gulf War, military
authorities have become increasingly concerned about the threat anthrax
and other biological warfare agents pose both to our armed forces and civilian
populations. "Anthrax is often fatal and easily dispersed through
air or water," Baker said. "We know that countries hostile to
the United States have developed strains of anthrax which are resistant
to antibiotics and existing vaccines. To counter that threat, the Defense
Advanced Research Projects Agency (DARPA), is testing several possible
new weapons against these biologic agents---including BCTP."
-
- "When properly formulated, the components
in BCTP form an emulsion of tiny lipid droplets suspended in solvent,"
said Wright. "These lipids fuse with anthrax spores causing the spore
to revert to its active bacterial state. During this process, which takes
four to five hours, the spore's tough outer membrane changes allowing BCTP's
solvent to strip away the exterior membrane. BCTP's detergent then degrades
the spore's interior contents. In scanning electron microscope images,
the spores appear to explode."
-
- In his conference presentation, Hayes
described how even low concentrations of BCTP killed more than 90 percent
of virulent strains of Bacillus anthracis spores in a culture dish. "We
observed sporicidal activity with dilutions as high as one part BCTP per
1,000 parts culture media," Hayes said.
-
- To determine its toxicity to animals,
U-M scientists fed large amounts of BCTP to laboratory rats and injected
mice with the material subcutaneously. The animals gained weight, remained
healthy and suffered no adverse effects.
-
- To determine BCTP's effectiveness at
treating animals exposed to anthrax spores, Baker's research team subcutaneously
injected mice with Bacillus cereus---a closely related species of bacteria
that can be safely handled in a university laboratory setting. Like B.
anthracis, its lethal relative, B. cereus produces large, ulcerous areas
of dead tissue if it penetrates the skin through a cut or injury. If untreated,
these skin infections spread systemically, producing severe illness and
death in 80 percent of the laboratory mice in the study.
-
- "When we washed the animal's skin
lesions with BCTP, the wounds began to heal," Baker said. Mice receiving
BCTP either simultaneously with B. cereus spores or whose wounds were washed
with BCTP an hour after exposure had a 95 percent reduction in lesion size.
The death rate for mice receiving BCTP was only 20 percent.
-
- "Rapid inactivation of anthrax bacteria
and spores combined with low toxicity makes BCTP a promising candidate
for use as a broad-spectrum, post-exposure decontamination agent,"
Baker said.
-
- In future studies, Baker plans to evaluate
BCTP's effectiveness against inhaled anthrax spores, as well as other bacteria
and enveloped viruses. His research has been funded by DARPA's Unconventional
Pathogen Countermeasures Program. The U-M and Novavax have filed a patent
application covering BCTP's use as a decontamination agent for various
anti-microbial applications. Baker is a member of the Novavax scientific
advisory board, but has no significant financial interest in the company.
-
- Contact: Sally Pobojewski Phone: (734)
647-1844 E-mail: pobo@umich.edu
-
- EDITORS: A black-and-white scanning electron
microscope image of anthrax spores before and after treatment with BCTP
is available on request. An announcement describing BCTP and the material's
anti-microbial properties is being released simultaneously today by Novavax,
Inc. _________________
-
- NOTE: In accordance with Title 17 U.S.C.
section 107, this material is distributed without profit or payment to
those who have expressed a prior interest in receiving this information
for non-profit research and educational purposes only. For more information
go to: http://www.law.cornell.edu/uscode/17/107.shtml -----------------------
-
- Drug "Blows
Apart" Bacteria
From BBC Sci/Tech
9-27-98
- Durg works by destroying bacteria
from the inside
-
- Scientists say they have found a new
drug that could kill a wide range of bacteria and viruses including the
deadly anthrax virus.
-
- The US company Novavax said the drug,
called BCTP, literally blows apart bacteria, without harming normal cells.
-
- "One of the most remarkable characteristics
of this material is its ability to rapidly destroy a wide variety of dangerous
bacteria and viruses, while remaining non-toxic to people, animals and
the environment," said one of the researchers, Dr James Baker of the
University of Michigan.
-
- The drug strips away the outer membrane
of a microbe and explodes its contents but does not harm other cells.
-
- The research suggests BCTP could be used
to counter the use of anthrax as a biological weapon.
-
- Fears that Iraq had stockpiled anthrax
bombs led to the inoculation of all American troops.
-
- When inhaled, anthrax spores kill quickly
and once the symptoms appear it is too late to treat them with antibiotics.
-
- Dr Baker's team tested mice infected
with a relative of anthrax known as Bacillus cereus. The mice developed
large areas of dead skin.
-
- "When we washed the animals' skin
lesions with BCTP, the wounds began to heal," he said, with the lesions
on the mice reduced by 95%.
-
- Killing from the inside
-
- Microbes like anthrax can be killed by
poisonous substances like bleach or formaldehyde. But the problem is that
they also kill healthy cells.
-
- BCTP is made up of a mixture of tiny
pieces of fats and chemicals. It is said to work by breaking down the tough
outer coat of a microbe, which is usually resistant to disinfectants.
-
- "BCTP's detergent then degrades
the spore's interior contents. In scanning electron microscope images,
the spores appear to explode," explained Dr Baker.
-
- The research was presented at the American
Society of Microbiology's annual ICAAC meeting on infectious diseases in
San Diego.
-
- Dr Baker's work is funded by Novavax
and by the US Defence Advanced Research Projects Agency, plans to test
the drug against inhaled anthrax spores.
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