Protecting Teeth
With Bacteria That Bite BackFriday, August 02,
2002Brush 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 cavities.
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 on teeth.
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 complete.
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 fewer
cavities.
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. |