Periodontal pathogen genome provides perspectives on evolution, gum disease

HOUSTON (Mar 29, 2004) - The Human Genome Sequencing Center at Baylor College of Medicine (BCM-HGSC) announced today the complete genome sequence of Treponema denticola, a bacterium associated with periodontal disease, the inflammation of gum tissue that frequently precedes tooth loss.

80% of adults in the U.S. have periodontal disease at some time in their lives and treatment involves intensive antibiotic therapy and surgery. Recent evidence suggests linkage between periodontal and cardiovascular diseases as well as pre-term birth/ low birth weight of infants and periodontal disease in the mother.

The results will appear in the April 13, 2004 issue of Proceedings of the National Academy of Sciences and are scheduled to be published online this week. The study was supported by the National Institute of Dental and Craniofacial Research of the U.S. National Institutes of Health and was conducted at the BCMHGSC, the University of Texas Health Science Center-Houston (UTHSCH) and The Institute for Genomic Research (TIGR).

The spirochete T. denticola lives in a biofilm, layers of microbes, located between the gum and tooth. Gingivitis and periodontitis occur when the balance of oral microbes is disturbed, and certain bacteria predominate, leading to oral diseases.

The co-Principal Investigators, George Weinstock of the BCM-HGSC and Steven J. Norris, of the UTHSCH, sequenced the syphilis-causing microbe Treponema pallidum in 1998 with TIGR, and found significant genomic differences between these evolutionary cousins. The TIGR team was led by Ian Paulsen, Rekha Seshadri, and Claire Fraser who also collaborated on the T. pallidum project.

This remarkable organism will provide insights into the normal human flora, the evolution of the spirochetes, and human disease. It is a bonanza of information said Dr. George Weinstock, Co-Director of the BCM-HGSC.

T. denticola has a genome nearly three times the size of T. pallidum, with a distinct composition of bases, the letters of the genetic code, indicating ancient divergence between the microbes. Nearly all T. pallidum proteins are encoded by T. denticola, whose extra genes allow it to survive in different environments than T. pallidum.

A major surprise revealed by the T. denticola genome sequence is the relative lack of biosynthetic machinery, says Norris. ents than T. pallidum. Although it has nearly three times the number of genes as its cousin, T. pallidum, it contains few genes for making important cellular components such as amino acids. Instead, it has an abnormally high number of degradative enzymes and transporters for scavenging nutrients from dental plaque. Since it lives in the equivalent of an auto salvage yard filled with dying host cells and millions of other bacteria, T. denticola apparently prefers to salvage the parts it needs rather making them itself. Some of these enzymes, such as proteases, damage cells that hold teeth in place.

Four spirochete genomes have been sequenced (Borrelia burgdorferi and Leptospira interrogans along with the treponemes) providing a remarkable opportunity to study evolution. This highlights the power of comparative genomics to help us understand how related pathogens can cause completely different diseases, says Ian Paulsen.

Compared to other spirochetes, T. denticola is relatively easy to cultivate and manipulate genetically, making this an excellent model for spirochete research. It is a potential workhorse for studying the more intractable microbes like T. pallidum.