Treponema denticola

Introduction

Treponema denticola are a long spiral-shaped, anaerobic bacteria commonly found in the mouth. T. denticola is a gram-negative bacterium, meaning they have a thin peptidoglycan layer and an outer lipid membrane. T. denticola is highly specialized to reside in the gum crevice of the oral cavity and is one of the bacterial species responsible for causing periodontal disease. 

Disease

 Periodontal disease, also known as gum disease, is a severe gum infection that affects the soft tissue surrounding teeth. T. denticola, Porphyromonas gingivalis, and Tannerella forsythia are known as the “red complex”. They are the three most common bacteria present in the biofilm (also known as plaque) associated with chronic periodontitis. Together, they help each other grow and thrive during infection. 

The disease begins with the accumulation of plaque around the teeth. If oral hygiene is poor, plaque can harden under the gum line and become tartar, which can only be removed by a dentist. With time, tartar can cause gingivitis, a reversible, mild version of periodontal disease. Severe periodontal disease occurs once gum tissue breaks down and pockets begin to develop between teeth and gums, filling up with even more plaque. 

The protein-degrading (proteolytic) enzymes secreted by T. denticola break down the host gum proteins. The lysis of gingival cells and subsequent inflammation are the primary causes of periodontitis. Symptoms of periodontitis include pain, redness, swelling, and bleeding of the gums, and a receding gum line. If left untreated, the damage caused by T. denticola can eventually lead to tooth loss and the spread of infection to the jaw bone. 

T. denticola has also been shown to promote oncogenesis, where healthy cells become cancer cells via genetic and/or cellular changes. A specific enzyme produced by T. denticola was identified in the majority of tumor samples and was shown to degrade regulatory proteins involved in the control of inflammation and tumor microenvironment. 

Figure 1. Tooth diagram showing the development of periodontal disease. Source: Mayo Foundation For Medical Education and Research.

Epidemiology 

Periodontal disease is one of the most common infectious diseases around the world. According to the Centers of Disease Control and Prevention, about 47% of all adults over 30 in the U.S. have some level of periodontal disease. The susceptibility also increases with age, with 70% of people over 65 having the disease. Other factors, such as smoking, medications, hormone changes, and underlying health conditions can also increase the risk of developing periodontitis. 

The mouth contains a wide range of natural microbiota. However, periodontal disease often results from the overgrowth of certain bacterial species that are also present in healthy individuals. In fact, studies have shown that it is possible to predict the development of periodontitis based on the abundance of different species, especially those of the Red Complex such as T. denticola

Good oral care including frequent brushing and flossing is the most effective preventative measure against periodontitis. Yearly dentist visits can also help prevent the progression of the disease by removing tartar and plaque that cannot be easily accessed with a toothbrush. 

Virulence factors

T. denticola has a variety of virulence factors that allow it to infect the host. One of the first steps of infection is attachment, and T. denticola cells are covered in a protein called major outer sheath protein, which can bind to many different host proteins. T. denticola has a very strong metabolic association with P. gingivalis. This means that both species can work together to break down proteins, share nutrients, and become overall more efficient. Studies have shown that when cultured together, biofilm formation is enhanced. Biofilm aids attachment to teeth and can help protect bacteria against environmental stress. 

Like other gram-negative bacteria, T. denticola can release small spherical vesicles filled with various molecules such as enzymes and toxins which further help invasion. When released into the environment, they can help break down the tight junctions between host cells and allow the bacterial cells to penetrate deeper tissues. Dentilisin is another very important virulence factor that aids in the progression of disease. It can destroy communication pathways and other structural host cell proteins. 

Once inside, bacteria can use their internalized flagella to swim deeper into the tissue. By being located under the outer sheath, the flagella are concealed from the immune system, avoiding recognition by antibodies. T. denticola can also respond to environmental changes by a process called chemotaxis. Bacteria can move towards different stimuli such as glucose, allowing them to make the most out of their surroundings.

The host’s body will try to fight off the infection to the best of its ability, but T. denticola has ways of suppressing immune responses. This is highly advantageous to T. denticola, as it can remain unnoticed for longer periods of time. Some epithelial cells produce antimicrobial peptides, which are molecules that inhibit different mechanisms and can lead to the destruction of bacterial cells. T. denticola can prevent these molecules from attaching to its outer membrane and therefore entering the cell. It can also pump out these molecules before they cause any damage. Dentilisin produced by T. denticola can also break down different cytokines which are used by the body to alert and activate the immune system. 

 Figure 2. Treponema pallidum. A) The syphilis causing bacterium, T. pallidum, belongs to the same genus as T. denticola. Both have the same spiral-shaped (spirochete) cell structure; B) Cellular components of a typical spirochete bacterium. Adapted from Peeling, et al., (2017). Syphilis. Nature Reviews Disease Primers, 3(1). https://doi.org/10.1038/nrdp.2017.73 

The treatment of T. denticola infections is dependent on how far the infection has spread. For acute infections that have not reached under the gum flaps, excessive plaque can be physically removed from teeth via scaling and a course of antibiotics. For infections that have spread below the gum line and around the root of the tooth, the area may be surgically cleaned and a tissue graft may be performed. This involves removing skin from the roof of the mouth and covering the areas affected by gumline recession caused by T. denticola. For extreme cases when the infection has spread to the bone, a bone graft may be performed. A bone graft procedure is performed by surgically removing the infected bone and then transplanting synthetic material or fragments of your own bone. This essentially “rebuilds” the jaw and allows the bones to regrow over the previously infected areas.

References

Centers for Disease Control and Prevention. (2013). Periodontal disease. Centers for Disease Control and Prevention. Retrieved November 18, 2021, from https://www.cdc.gov/oralhealth/conditions/periodontal-disease.html. 

Dashper, S. G., Seers, C. A., Tan, K. H., & Reynolds, E. C. (2010). Virulence factors of the oral spirochete Treponema denticola. Journal of Dental Research, 90(6), 691–703. https://doi.org/10.1177/0022034510385242 

Foschi, F., Izard, J., Sasaki, H., Sambri, V., Prati, C., Müller, R., & Stashenko, P. (2006). Treponema denticola in disseminating endodontic infections. Journal of dental research, 85(8), 761-765.

Inagaki, S., Kimizuka, R., Kokubu, E., Saito, A., & Ishihara, K. (2016). Treponema denticola invasion into human gingival epithelial cells. Microbial Pathogenesis, 94, 104–111. https://doi.org/10.1016/j.micpath.2016.01.010 

Ishihara, K. (2010). Virulence factors of Treponema denticola. Periodontology 2000, 54(1), 117–135. https://doi.org/10.1111/j.1600-0757.2009.00345.x 

Loesche, W. J., & Grossman, N. S. (2001). Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clinical microbiology reviews, 14(4), 727-752.

Mayo Foundation for Medical Education and Research. (n.d.). Periodontitis. Mayo Clinic. Retrieved November 18, 2021, from https://www.mayoclinic.org/diseases-conditions/periodontitis/symptoms-causes/syc-20354473. 

Nazir M. A. (2017). Prevalence of periodontal disease, its association with systemic diseases and prevention. International journal of health sciences, 11(2), 72–80.

Nieminen, M., Listyarifah, D., Hagström, J. et al. 2017. Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation. Br J Cancer 118, 428–434 (2018). https://doi.org/10.1038/bjc.2017.409

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