Finding the Hole in the Defenses of Cavity-Creating Microbes
June 25, 2004
"Within an hour after you eat, you can run your tongue over your teeth and feel a sort of film. That’s plaque – really, a community of bacteria making themselves comfortable for a long-term stay in your mouth."
Forcing the bacteria in our mouths to choke on their own acids may offer one way to stop cavities, say microbiologists at the University of Rochester Medical Center who have discovered a chink in the armor that bacteria use to survive the hostile environment of the human mouth.
Streptococcus mutans or S. mutans, the dominant bacterium in our mouths, latches onto teeth, eats sugar, and then secretes acid, making the bacteria the number-one cause of tooth decay around the world. The secret of its success? The bacterium rearranges its cell membranes to make itself impervious to the acid assault that it lets loose.
“Right now there are millions of bacteria in your mouth, eating sugars and excreting acid which is eating your teeth,” says Robert Quivey Jr., Ph.D., a microbiologist and an associate professor in the Center for Oral Biology. “That’s why proper oral hygiene, such as brushing, flossing and regular dental check-ups, are so important, to rid the mouth of these bacteria.”
In a paper in the July 1 issue of the Journal of Bacteriology, Quivey and graduate student Elizabeth Fozo discuss a vulnerability of S. mutans, a bug that infects almost everyone. Scientists have known for some time that the microbe specially modifies itself once it starts producing acid in the mouth. The Quivey group has shown that the changes include shuffling fatty acids in its membrane – much like a bricklayer might move bricks to fortify a fence – so it can withstand the wash of acids that it sends pouring into the mouth.
The Rochester team found that a gene known as fabM is responsible for changing the membrane’s composition and enables S. mutans to become more resistant to acid. The same gene had previously been discovered in a similar bug that causes a type of virulent pneumonia, in research by a group led by Charles Rock at St. Jude Children’s Research Hospital in Memphis
When Fozo and Quivey knocked out the gene in S. mutans, the bacteria’s defenses fell; the cell membrane was no longer able to protect against the acid the bacteria churn out.
“These bacteria should not be able to live in the mouth,” says Quivey, “but they adapt to the acidic environment and thrive, thanks to the special defenses they use. Not only that, but the acid they produce harms other bacteria, allowing S. mutans to dominate. We’re trying to make the human mouth, the only hospitable environment that S. mutans has ever found, inhospitable.”
S. mutans is one of hundreds of types of bacteria in the human mouth. When people eat sugary foods, S. mutans eats the sugars, coats the teeth, excretes acids, and forms a pudding-like goo – plaque – that consists of bacteria, sugars, and other substances all locked together in a matrix that sticks to teeth. As the crowd of bacteria gathers, it becomes tough for saliva, a healthful substance that bathes the teeth in nutrients and fights cavities, to reach and cleanse the teeth.
“Within an hour after you eat, you can run your tongue over your teeth and feel a sort of film. That’s plaque – really, a community of bacteria making themselves comfortable for a long-term stay in your mouth. It can really get disgusting in there,” says Quivey.”
With S. mutans comfortably lodged along our tooth surfaces, the pH in our mouths quickly plummets, becoming 100 to 1,000 times more acidic than normal. Without frequent brushing and flossing, the assault on our teeth results in cavities quickly.
Like S. mutans, other bacteria have the ability to change their cell membranes to cope with harsh conditions. E. coli bacteria happily ensconced in red meat perform a similar trick as they travel through the human digestive system. Another harmful bacterium, Listeria, changes its membrane properties to allow it to live even in the cool temperatures of the refrigerator.
Matching the bacteria’s abilities, however, are various human strategies to kill the microbes. Many current antibiotics focus on cell membranes; other compounds exist that target the cell membranes to wipe out S. mutans, but those compounds are also toxic to humans. FabM offers a target that is present in S. mutans but not in humans, Quivey says. By taking advantage of FabM, it may be possible to kill the bacteria – and reduce cavities.
“We’ve identified a potentially useful and novel pathway, but we have a very long road to go to identifying and isolating a compound that stops the process in bacteria,” says Quivey, who is also on the faculty of the Eastman Department of Dentistry and the Department of Microbiology and Immunology. “I’m cautiously optimistic.”
The research, which was funded by the National Institute for Dental and Craniofacial Research, earned a prize for Fozo at the spring meeting of the International Association for Dental Research in Hawaii.