Wash that mouth out with bacteria!

A spoonful of sugar may make the medicine go down, but it also provides a feast for Streptococcus mutans. This bacterium, the primary cause of tooth decay, colonizes the teeth of almost everyone by age 3. Nourished by sugar, the microbe produces lactic acid, which destroys tooth enamel, leading to the lesions known as caries or cavities.

A few scientists have long pursued the idea of eliminating tooth decay by replacing the destructive strain of S. mutans with a harmless one. In the February INFECTION AND IMMUNITY, Jeffrey D. Hillman of the University of Florida College of Dentistry in Gainesville and his colleagues describe a genetically engineered version of the microbe that may fit the bill.

If the Food and Drug Administration approves the group's proposal, the researchers could begin human safety tests of the bacterium this year.

Called replacement therapy, the strategy of swapping bad bacteria in a person for safe ones dates back more than a century. Louis Pasteur discussed the merits of the approach, notes Hillman. Scientists have had little success with it, however. The main difficulty has been finding in nature a harmless strain that can displace the pathogenic form of a bacterium. In the case of S. mutans, for example, "whatever strain gets there first has an edge," explains Hillman.

The researchers decided to create a replacement strain with a clear advantage. They started with a naturally occurring S. mutans strain that secretes a chemical compound that kills other forms of the microbe. The Florida scientists found that this murderous strain can safely displace a natural S. mutans population.

They next crippled this bacterium's lactic acid production by disabling the gene for a crucial enzyme. Unable to make lactic acid, however, the microbes suffered a lethal buildup of toxic products from their altered metabolism. So, the investigators further modified the S. mutans strain by adding an extra copy of a gene for an enzyme designed to break down the toxic compounds. Voila, a strain that made no lactic acid but still thrived. In rats, replacement therapy using this strain stopped tooth decay, even when the animals ate a high-sugar diet.

Would people allow dentists to squirt genetically engineered bacteria into their mouths? Hillman stresses that while fluoride and better dental-hygiene practices have slashed the rate of tooth decay among children, it remains a huge problem, especially as people live longer. "Tooth decay is still one of the most costly infectious diseases we have," he says, noting that people in the United States spend more than $50 billion a year on the condition.

Hillman's team must rigorously prove the safety of its strain, warns Robert E. Marquis of the University of Rochester (N.Y.) Medical Center, who has also looked into S. mutans replacement therapy. On rare occasions, he notes, the natural microbe escapes into the blood and causes dangerous heart infections. Hillman's group has indeed begun to check whether its replacement strain is more or less likely to do the same.

Even if S. mutans replacement therapy doesn't become widespread, Hillman hopes that proving its feasibility will prompt scientists to try the approach with more dangerous bacteria, such as the ones that cause meningitis. "There's a long list of bacterial infections that are approachable with replacement therapy," he says.