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9-Misc: Protecting teeth with GE bacteria



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TITLE:  Protecting Teeth With Bacteria That Bite Back
SOURCE: The Washington Post, USA, by Rick Weiss
        http://www.washingtonpost.com/wp-dyn/articles/A41876-2002Jul21.html
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 
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.



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