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ATHENS, Ga. -- Scientists at the University of Georgia have discovered that an enzyme in a common bacterium is capable of activating blood-clotting in the human body. This is the first reported evidence of such an effect and may help explain the link between periodontal infections and heart disease.
The new knowledge could lead to a vaccine that might neutralize the enzyme before it has a chance to activate blood-clotting and lead to cardiovascular diseases, a not uncommon occurrence in individuals with periodontitis.
"Periodontal disease is the number-one chronic infectious disease in the world," said Dr. James Travis, a professor of biochemistry and molecular biology who led the research team at UGA. "We believe it will be possible to make an inhibitor that will stop this enzyme in its tracks."
The study was published today in the the Journal of Biological Chemistry and was supported by the National Institutes of Health and by a grant from the Committee of Scientific Research in Poland.
The bacterium is known as Porphyromonas gingivalis, and it is a cause of adult periodontal disease, an infectious condition associated with a loss of connective tissue, resorption of bone and formation of infectious pockets. It is the most common cause of tooth loss in adults and is called an "opportunistic anaerobe" -- an organism living without oxygen and waiting to receive nutrition. Though the full reason for periodontitis remains unclear, it clearly has a close relationship with P. gingivalis infections.
Two similar forms of the enzymes produced by the bacterium are called gingipain Rs, and the team at UGA suspected they might be involved in causing blood clots. They also suspected an involvement with thrombin, a body chemical that cleaves a blood-plasma protein called fibrinogen into the insoluble protein referred to as a fibrin clot.
"Though snake-venom enzymes have been found to activate clotting, this is the first bacterial enzyme found to perform this same function," said Travis.
But while the formation of blood clots is an important defense against cuts and bruises, blood-clotting can also be a serious problem in the cardiovascular system and can lead to such diseases as phlebitis or even heart attacks.
A number of studies have shown a link between mouth infections and heart disease. A report in the journal Science on April 11 revealed that in research involving 1,372 Pima Indians in Arizona, those with periodontal disease were 2.7 times as likely to suffer a heart attack as were those with healthy gums. This research, conducted by scientists at the State University of New York at Buffalo, was among the first to exclude smoking as a potential cause of gum disease, since few of the Indians in the study smoked.
The report in Science said that "Researchers must still elucidate the connection between gum and heart problems." The research by Travis and his team is the first to suggest a mechanism for the linkage.
In the laboratory, Travis and colleagues measured the clotting time of both whole blood and blood plasma when exposed to gingipain Rs. They found in two separate tests (activated partial thromboplastin time and prothrombin time) that blood-clotting time was "markedly reduced" in the presence of gingipain Rs. They also discovered that these bacterial enzymes (proteinases) may be a cause of blood-clotting in a systemic, blood-borne pathogenic condition known as sepsis.
"The coagulation system is part of a tighly regulated pathway involving many enzymes," said Travis. "It has a so-called cascade pathway in the body, meaning that one enzyme turns on another, and then another and so forth. Normally these enzymes are present in an inactive form and are only activated when coagulation is required."
While the discovery is good news in potentially breaking the link between gum disease and heart disease, Travis said that P. gingivalis has a phenomenal ability to evade host defenses and even uses host enzymes for its own growth. In essence, it is telling the host to "kill me" and then evading the body's response and actually degrading host tissue.
The gene structure of P. gingavalis is nearly complete, and that knowledge may offer inviting targets for intervention from vaccines.
While periodontal disease is common in the U.S., particularly among the elderly, it is far worse in Third World countries, though its role in the development of cardiovascular disease in those countries is not yet clear.
University of Georgia. June 1997.
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