9-Misc: Protecting teeth with GE bacteria
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- Date: Wed, 24 Jul 2002 09:53:11 +0200
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TITLE: Protecting Teeth With Bacteria That Bite Back
SOURCE: The Washington Post, USA, by Rick Weiss
DATE: July 22, 2002
------------------ archive: http://www.gene.ch/genet.html ------------------
Protecting Teeth With Bacteria That Bite Back
Brush your teeth after every meal. Floss regularly. And be sure to keep
your teeth nicely coated with a film of genetically engineered bacteria.
That's the advice dentists might offer if scientists achieve their goal of
enlisting custom-designed bacteria in the war against tooth decay. The aim
is to use an army of gene-altered microbes to rid the mouth of bacteria
that cause cavities, effectively shifting the balance of power in the bug-
eat-bug world of oral ecology.
"Our strain can be just brushed onto the tooth surface or squirted into
someone's mouth, and it will elbow out any other strain" of cavity-causing
bacteria, said Jeffrey Hillman of the University of Florida College of
Dentistry. Hillman is one of several researchers to have engineered tooth-
friendly versions of the bacteria that cause tooth decay.
Scientists in this field say their work has therapeutic potential beyond
dental hygiene. Chronic low-grade bacterial infections cause or contribute
to many ailments, such as ulcers and heart attacks. If those harmful
bacteria could be displaced by others engineered to be benign, the need for
antibiotics and other drugs might be greatly reduced.
The strategy carries risks, however. Ecological disruption -- even on the
microscopic scale -- often results in unexpected consequences.
And then there is the public relations problem that could arise if
consumers were to perceive an unsavory alliance between dentistry ("This
won't hurt a bit!") and genetic engineering.
"You don't need me to tell you that you're likely to run into some
opposition, when you see statements out of Europe calling genetically
modified food 'Frankenfood,' " said William H. Bowen of the University of
Rochester Medical Center, who has helped develop designer bacteria against
Bowen says he's not yet convinced that tooth decay is a disease serious
enough to justify coating people's teeth with gene-altered bacteria.
But, he said, the work is sure to deepen scientists' understanding of
biofilms -- thin but complex communities of protein, carbohydrates and
bacteria. Research indicates that many bacteria that are benign on their
own can cause medical problems when they become part of a biofilm, and
scientists want to understand how bacteria in these environments interact
with each other and with the body.
"Dental plaque is a beautiful biofilm model," Bowen said. "It's a wonderful
research tool that can help us understand other bacterial diseases."
The human mouth is home to billions of bacteria belonging to more than 300
species, but one species is the major cause of tooth decay. The culprit is
Streptococcus mutans, a spherical bacterium that thrives on the organic
film that coats tooth surfaces and makes an enzyme called lactate
dehydrogenase (LDH). That enzyme converts food sugars into lactic acid, a
corrosive chemical that gradually dissolves the protective enamel coating
Microbial gene jockeys are experimenting with at least three methods for
blocking this biochemical ticket to the dentist's chair. In one approach,
researchers in England and Sweden have created gene-altered versions of a
harmless bacterium called Lactobacillus zeae, a relative of the bacterium
found in yogurt.
The team put into those bacteria a new gene that allows the microbes to
make monoclonal antibodies -- biochemical entities specifically designed to
attach themselves to the surface of S. mutans.
The antibodies grabbed free-floating S. mutans bacteria in saliva and gave
them "a kiss of death," said lead researcher Lennart Hammarstrom of the
Karolinska Institute's Center for Oral Biology in Huddinge, Sweden.
In laboratory research published in the July issue of Nature Biotechnology,
rats that had the altered Lactobacilli swabbed on their teeth every other
day for three weeks and were fed a diet of very sweet drinks developed
about 40 percent fewer early cavities than those that had a control
solution swabbed on their teeth and were fed the same diet.
"If this actually works in people, then there would be a large number of
potential applications," Hammarstrom said, in which Lactobacillus would be
engineered to make antibodies against other targets.
Taking a different approach, Hillman of Florida has created a strain of S.
mutans that lacks the LDH gene and is incapable of producing lactic acid.
Hillman's strain also secretes a natural antibiotic that kills conventional
S. mutans without harming other oral bacteria, ensuring that it will
dominate its disease-causing cousins. Experiments showed a significant
reduction in cavities in rats whose mouths were colonized with the bacteria.
Hillman said he has recently improved the strain to reduce the chances that
it would regain the ability to make lactic acid -- or worse, develop an
enhanced ability to do so. In an effort to gain Food and Drug
Administration permission to conduct the first tests in people, he has
added a gene that makes his bacteria dependent on a synthetic nutrient that
is not normally in the human diet.
Study subjects would have to rinse their mouths periodically with a
solution containing the nutrient or the engineered bacteria would die -- an
extra level of assurance for those who fear the consequences of releasing
gene-altered bacteria into the environment. Hillman said he expects that
the extra precaution will be unnecessary after initial safety studies are
Many questions will have to be answered before such biological warriors are
unleashed in large-scale tests. How long do engineered bacteria survive in
the mouth? Some evidence suggests that a dose in early childhood could last
a lifetime. What would be their impact on other oral bacteria?
Lawrence Tabak, director of the National Institute of Dental and
Craniofacial Research, said the European team's plan to use bacterially
made antibodies to kill S. mutans in the mouth could open a niche into
which even worse bacteria might move. He would rather replace harmful S.
mutans with a species engineered to be friendly -- perhaps even one that
would enhance the body's methods for rebuilding tooth surfaces.
"Some microorganisms produce acids, but others produce bases, and these
bases provide a milieu that favors remineralization," a natural buildup of
tooth enamel, Tabak said. "The processes of tooth decay and
remineralization are very dynamic processes, and we now have a whole host
of tools to look at this in real time."
Robert Burne of the University of Florida has pioneered just such an
approach. Burne has developed strains of S. mutans that have been endowed
with a gene to increase production of an enzyme called urease. That enzyme
converts urea into ammonia, a base, creating conditions conducive to making
enamel. Rats whose mouths were colonized with Burne's bacteria strains got
Of course, that doesn't mean it will work in people. And even if it does,
it might not sell. Getting people to gargle with microbial mouthwash might
be like pulling teeth.
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