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'''''Treponema denticola''''' is a [[Gram-negative]], [[obligate anaerobic]], motile and highly proteolytic [[spirochete]] bacterium. It is one of four species of oral spirochetes to be reliably cultured, the others being ''Treponema pectinovorum, [[Treponema socranskii]]'' and ''[[Treponema vincentii]]''<ref name=":1">{{cite journal | vauthors = Chan EC, McLaughlin R | title = Taxonomy and virulence of oral spirochetes | journal = Oral Microbiology and Immunology | volume = 15 | issue = 1 | pages = 1–9 | date = February 2000 | pmid = 11155157 | doi = 10.1034/j.1399-302x.2000.150101.x }}</ref>''.      T. denticola'' dwells in a complex and diverse microbial community within the oral cavity and is highly specialized to survive in this environment. ''T. denticola'' is associated with the incidence and severity of human [[periodontal disease]].  ''Treponema Denticola'' is one of three bacteria that form the Red Complex, the other two being ''[[Porphyromonas gingivalis]]'' and ''[[Tannerella forsythia]]''. Together they form the major virulent pathogens that cause chronic [[Periodontal disease|periodontitis]].<ref name=":0">{{cite journal | vauthors = Öğrendik M | title = Periodontal Pathogens in the Etiology of Pancreatic Cancer | journal = Gastrointestinal Tumors | volume = 3 | issue = 3-4 | pages = 125–127 | date = March 2017 | pmid = 28611978 | pmc = 5465713 | doi = 10.1159/000452708 }}</ref> Having elevated ''T. denticola''  levels in the mouth is considered one of the main etiological agents of [[periodontitis]].<ref name=Jobin2008>{{cite book | title = Molecular Oral Microbiology |editor1=Anthony H. Rogers | publisher=Caister Academic Press | year = 2008 | authors=Marie-Claude Jobin, Mohsen Amin, Richard P. Ellen |chapter=Chapter 8 - The Molecular Biology of the Survival and Virulence of ''Treponema denticola'' |page=177| isbn=978-1-904455-24-0}}</ref><ref>{{cite journal | vauthors = Simonson LG, Goodman CH, Bial JJ, Morton HE | title = Quantitative relationship of Treponema denticola to severity of periodontal disease | journal = Infection and Immunity | volume = 56 | issue = 4 | pages = 726–8 | date = April 1988 | pmid = 3346072 | pmc = 259361 | doi = 10.1128/IAI.56.4.726-728.1988 }}</ref> ''T. denticola'' is related to the syphilis-causing obligate human pathogen, ''[[Treponema pallidum]]'' subsp. ''pallidum''. It has also been isolated from women with [[bacterial vaginosis]].<ref name="AfricaNel2014">{{cite journal | vauthors = Africa CW, Nel J, Stemmet M | title = Anaerobes and bacterial vaginosis in pregnancy: virulence factors contributing to vaginal colonisation | journal = International Journal of Environmental Research and Public Health | volume = 11 | issue = 7 | pages = 6979–7000 | date = July 2014 | pmid = 25014248 | pmc = 4113856 | doi = 10.3390/ijerph110706979 }}</ref>
'''''Treponema denticola''''' is a [[Gram-negative]] [[anaerobic]] [[spirochete]] bacterium that is commonly found in the human oral cavity. It is one of the main [[pathogens]] associated with [[periodontal disease]], a chronic inflammatory condition affecting the tissues surrounding the teeth.


== Genome ==
==Morphology==
The first genome of ''T. denticola'' to be sequenced was strain 35405 which was initially isolated and designated as the type strain by Chan et al.<ref>{{cite journal | vauthors = Chan EC, Siboo R, Keng T, Psarra N, Hurley R, Cheng SL, Iugovaz I | title = Treponema denticola (ex Brumpt 1925) sp. nov., nom. rev., and identification of new spirochete isolates from periodontal pockets | journal = International Journal of Systematic Bacteriology | volume = 43 | issue = 2 | pages = 196–203 | date = April 1993 | pmid = 8494734 | doi = 10.1099/00207713-43-2-196 | doi-access = free }}</ref> The 2,843,201-bp genome sequence encodes 2,786􏴲 [[open reading frame]]s  (ORFs) as well a 6 [[Ribosomal RNA|rRNAs]] and 44 [[Transfer RNA|tRNAs]]. This is in stark contrast to the minimal genome of ''[[Treponema pallidum]]'' which encodes only 1,040 ORFs.<ref>{{cite journal | vauthors = Seshadri R, Myers GS, Tettelin H, Eisen JA, Heidelberg JF, Dodson RJ, Davidsen TM, DeBoy RT, Fouts DE, Haft DH, Selengut J, Ren Q, Brinkac LM, Madupu R, Kolonay J, Durkin SA, Daugherty SC, Shetty J, Shvartsbeyn A, Gebregeorgis E, Geer K, Tsegaye G, Malek J, Ayodeji B, Shatsman S, McLeod MP, Smajs D, Howell JK, Pal S, Amin A, Vashisth P, McNeill TZ, Xiang Q, Sodergren E, Baca E, Weinstock GM, Norris SJ, Fraser CM, Paulsen IT | display-authors = 6 | title = Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 15 | pages = 5646–51 | date = April 2004 | pmid = 15064399 | pmc = 397461 | doi = 10.1073/pnas.0307639101 | bibcode = 2004PNAS..101.5646S }}</ref>
''Treponema denticola'' is characterized by its unique [[helical]] shape, typical of spirochetes. It is a slender, tightly coiled bacterium, approximately 0.2 to 0.5 micrometers in diameter and 6 to 15 micrometers in length. The bacterium is motile, possessing [[endoflagella]] that run along the length of the cell, allowing it to move in a corkscrew motion.


== Cell structure ==
==Genomic Characteristics==
The native cellular architecture of the bacterial cell was revealed using [[cryo-electron tomography]], a technique observing intact plunge-frozen cells.<ref name="Izard_2008">{{cite journal | vauthors = Izard J, Hsieh CE, Limberger RJ, Mannella CA, Marko M | title = Native cellular architecture of Treponema denticola revealed by cryo-electron tomography | journal = Journal of Structural Biology | volume = 163 | issue = 1 | pages = 10–7 | date = July 2008 | pmid = 18468917 | pmc = 2519799 | doi = 10.1016/j.jsb.2008.03.009 }}</ref> Tightly organized bundles of periplasmic flagella were observed in the periplasm, a characteristic of spirochetes. The presence of the periplasmic flagella is widely regarded as being responsible for the microorganism’s ability to rotate and flex, in addition to its translational movement.<ref name=":1" /> [[Spirochaete|Spirochetes]], including ''Treponema denticola'' , are therefore able to navigate through particularly viscous environments, unlike that of other prokaryotes.<ref name=":1" />
The genome of ''Treponema denticola'' has been fully sequenced, revealing a circular chromosome of approximately 2.8 million base pairs. The genome encodes for a variety of [[proteins]] involved in [[metabolism]], [[virulence]], and [[motility]]. Notably, ''T. denticola'' possesses genes for [[proteolytic enzymes]] that degrade host tissues and [[immune evasion]] mechanisms.


The tapering of the cell ends, conserved between cells, encompass a patella-shaped structure observed in the periplasm at the cell tip. This structure might be involved in the polar attachment of the cells.<ref>{{cite journal | vauthors = Ellen RP, Dawson JR, Yang PF | title = Treponema denticola as a model for polar adhesion and cytopathogenicity of spirochetes | journal = Trends in Microbiology | volume = 2 | issue = 4 | pages = 114–9 | date = April 1994 | pmid = 8012753 | doi = 10.1016/0966-842x(94)90597-5 }}</ref> Cytoplasmic filaments, a bacterial intermediate-like filaments composed of the protein [[Prokaryotic cytoskeleton|CfpA]], are adjacent to the inner membrane and run parallel to the tightly organized flagellar filaments.<ref name="Izard_2008" /><ref>{{cite journal | vauthors = Izard J, McEwen BF, Barnard RM, Portuese T, Samsonoff WA, Limberger RJ | title = Tomographic reconstruction of treponemal cytoplasmic filaments reveals novel bridging and anchoring components | journal = Molecular Microbiology | volume = 51 | issue = 3 | pages = 609–18 | date = February 2004 | pmid = 14731266 | doi = 10.1046/j.1365-2958.2003.03864.x | url = https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1358&context=foodsciefacpub | doi-access = free }}</ref> Those cytoplasmic filaments are critical for pathogenicity, directly or indirectly as they are also involved in chromosome structure, segregation, or the cell division processes.<ref>{{cite journal | vauthors = Izard J, Sasaki H, Kent R | title = Pathogenicity of Treponema denticola Wild-Type and Mutant Strain Tested by an Active Mode of Periodontal Infection Using Microinjection | journal = International Journal of Dentistry | volume = 2012 | pages = 549169 | date = 2012 | pmid = 22829826 | pmc = 3398590 | doi = 10.1155/2012/549169 }}</ref><ref>{{cite journal | vauthors = Izard J, Samsonoff WA, Limberger RJ | title = Cytoplasmic filament-deficient mutant of Treponema denticola has pleiotropic defects | journal = Journal of Bacteriology | volume = 183 | issue = 3 | pages = 1078–84 | date = February 2001 | pmid = 11208807 | pmc = 94976 | doi = 10.1128/JB.183.3.1078-1084.2001 | citeseerx = 10.1.1.488.5178 }}</ref> The absence of either flagella or cytoplasmic filaments in deficient mutant increase the mouse peritoneal macrophages in vitro uptake.<ref>{{cite journal | vauthors = Gaibani P, Vocale C, Ambretti S, Cavrini F, Izard J, Miragliotta L, Pellegrino MT, Sambri V | display-authors = 6 | title = Killing of Treponema denticola by mouse peritoneal macrophages | journal = Journal of Dental Research | volume = 89 | issue = 5 | pages = 521–6 | date = May 2010 | pmid = 20200417 | pmc = 2868591 | doi = 10.1177/0022034510363105 }}</ref>
==Pathogenicity==
''Treponema denticola'' is a key component of the [[red complex]], a group of bacteria strongly associated with [[periodontitis]]. It contributes to disease through several mechanisms:


== Adherence and Cytotoxicity ==
* '''Adhesion''': ''T. denticola'' adheres to [[host cells]] and [[extracellular matrix]] components using [[adhesins]].
The main site for ''T. denticola'' habitation in the oral cavity is the [[Gingival sulcus|gingival crevice]]. These spirochetes attach to proteins (including [[fibronectin]] and [[collagen]]) of local gingival fibroblasts, binding to their plasma membrane. A 53-kDa surface protein on ''T. denticola'' is responsible for transporting its components into the host cell, exhibiting a cytotoxic effect. Accumulation of ''T. denticola'' in this manner facilitates the disease-causing process, including membrane blebbing and red blood cell lysis.<ref name=":1" />
* '''Invasion''': The bacterium can invade [[gingival epithelial cells]], disrupting cell junctions and penetrating deeper tissues.
* '''Tissue Destruction''': It produces [[proteases]] such as [[dentilisin]], which degrade [[collagen]] and other structural proteins.
* '''Immune Modulation''': ''T. denticola'' can modulate the host [[immune response]], evading detection and promoting chronic inflammation.


== Role in Disease ==
==Clinical Significance==
''Treponema denticola'' is implicated in the progression of periodontal disease, which can lead to [[tooth loss]] and has been associated with [[systemic conditions]] such as [[cardiovascular disease]] and [[diabetes mellitus]]. Detection of ''T. denticola'' in subgingival plaque is often used as a diagnostic marker for periodontal disease.


=== Periodontal Disease ===
==Diagnosis==
[[Periodontal disease]] is a type of gum disease caused by the accumulation of plaque on the teeth due to poor oral hygiene. [[Dental plaque|Plaque]] is a sticky substance that contains bacteria which can harden into a substance called [[Calculus (dental)|calculus]], irritating the gums.<ref>{{Cite web|url=http://www.sdcep.org.uk/published-guidance/periodontal-management/|title=Periodontal Care|website=SDCEP|language=en|access-date=2019-12-11}}</ref>
Diagnosis of ''Treponema denticola'' infection is typically performed using:


<ref>{{cite journal | vauthors = Sela MN | title = Role of Treponema denticola in periodontal diseases | journal = Critical Reviews in Oral Biology and Medicine | volume = 12 | issue = 5 | pages = 399–413 | date = 2001 | pmid = 12002822 | doi = 10.1177/10454411010120050301 }}</ref>''Treponema denticola'', a subgingival oral spirochete has been associated with many [[periodontal disease]] conditions such as: the early stage of periodontitis, acute pericoronitis (infection under the gum tissue covering a partially erupted tooth)<sup>3</sup>, as well as necrotising ulcerative gingivitis (severe inflammation of the gum more common in immunocompromised patients). It relates to lesions limited to [[Gums|gingival tissue]].<ref>{{Cite web|url=http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf|title=Management of acute dental problems. Guidance for healthcare professionals}}</ref>
* '''[[Polymerase Chain Reaction (PCR)]]''': Highly sensitive and specific for detecting ''T. denticola'' DNA in clinical samples.
* '''[[Microscopy]]''': Dark-field or phase-contrast microscopy can visualize the spirochete's characteristic morphology.
* '''[[Culture]]''': Although challenging due to its fastidious nature, ''T. denticola'' can be cultured under anaerobic conditions.


Clinical evidence and research shows that periodontal pockets contain large numbers of ''treponema denticola'' together with other proteolytic [[Gram-negative bacteria|gram negative bacteria]], playing an important role in the development of [[periodontal disease]]. The toxic products of these bacteria, especially ''treponema denticola'' may damage the surface lining periodontal cells making them more prone to damage as well as lysis. ''Treponema denticola'' attaches to [[fibroblast]]s and epithelial cells as well as to extracellular matrix components which are found in periodontal tissues and release its own bacterial contents. The bacterial components are:{{cn|date=January 2021}}
==Treatment==
* Outer sheath associated peptidases
Management of infections involving ''Treponema denticola'' includes:
* Chymotrypsin proteinases
* Trypsin proteinases
* Hemolytic activities
* Hemagglutinating activities
* outer-sheath protein with pore-forming properties


A number of studies have observed an increase of ''T. denticola'' in patients with orthodontic appliances, particularly the fixed type.<ref>{{cite journal | vauthors = Lucchese A, Bondemark L, Marcolina M, Manuelli M | title = Changes in oral microbiota due to orthodontic appliances: a systematic review | journal = Journal of Oral Microbiology | volume = 10 | issue = 1 | pages = 1476645 | date = January 2018 | pmid = 29988826 | pmc = 6032020 | doi = 10.1080/20002297.2018.1476645 }}</ref>
* '''[[Antibiotics]]''': Metronidazole and doxycycline are commonly used to target anaerobic bacteria.
* '''[[Mechanical Debridement]]''': Scaling and root planing to remove subgingival plaque and calculus.
* '''[[Antimicrobial Mouth Rinses]]''': Chlorhexidine gluconate can reduce bacterial load.


=== Oral Cancer ===
==Research Directions==
''Treponema Denticola'' is a potential etiological bacterial agent for [[oral cancer]].<ref name="Nieminen 428–434">{{cite journal | vauthors = Nieminen MT, Listyarifah D, Hagström J, Haglund C, Grenier D, Nordström D, Uitto VJ, Hernandez M, Yucel-Lindberg T, Tervahartiala T, Ainola M, Sorsa T | display-authors = 6 | title = Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation | journal = British Journal of Cancer | volume = 118 | issue = 3 | pages = 428–434 | date = February 2018 | pmid = 29149107 | pmc = 5808028 | doi = 10.1038/bjc.2017.409 }}</ref> It encourages [[oncogenesis]] (process in which healthy cells become cancer cells) and therefore the progression of oral cancer through chronic inflammation advancing invasiveness of the cancer cells. This results in the ceasing of cell [[apoptosis]] (inhibition of controlled cell death – a safety mechanism within cells to stop more damage from occurring), resulting in rapid growth and multiplication of cancer cells. This suppresses the immune system stopping the body from recognising the cancerous cells and as a result more cancer-promoting substances are produced.<ref name="Nieminen 428–434"/>  The presence of ''T. Denticola'' along with other periodontal pathogens and bacterial diversity within the oral cavity are important factors contributing to cancerous cells (including precancerous gastric lesions).<ref>{{cite journal | vauthors = Zhang WL, Wang SS, Wang HF, Tang YJ, Tang YL, Liang XH | title = Who is who in oral cancer? | journal = Experimental Cell Research | volume = 384 | issue = 2 | pages = 111634 | date = November 2019 | pmid = 31541617 | doi = 10.1016/j.yexcr.2019.111634 }}</ref>
Ongoing research is focused on understanding the molecular mechanisms of ''Treponema denticola'' pathogenicity and its interactions with other oral microbiota. Novel therapeutic approaches, including [[vaccines]] and [[probiotics]], are being explored to prevent and treat periodontal disease.


=== Vascular Disease ===
==See Also==
[[Atherosclerotic vascular disease]] is chronic inflammatory disease of large arteries distinguished by invasion, proliferation and accumulation of cells from arterial smooth muscle cells, and the circulating blood in the intimal layer with deposition of connective tissue and lipids, if left to get worse atherosclerotic vascular disease can result in cardiovascular disease. [[Cardiovascular disease]] (including angina, heart attack, arrhythmias, heart failure, strokes) is the leading cause of death globally.  {{cn|date=January 2021}}
* [[Periodontal disease]]
 
* [[Spirochaetes]]
Substantial evidence between inflammation from infectious agents and development of [[atherosclerosis]] – periodontal pathogens prominent contenders due to chronic inflammation related with [[periodontal disease]].{{cn|date=January 2021}}
* [[Oral microbiome]]
 
==External Links==
''Treponema Denticola'' bacteria can penetrate gingival tissues and circulate through blood vessels, with opportunity to invade the heart and cardiovascular epithelium in medium to large arteries – including aorta, coronary and carotid arteries.<ref>{{cite journal | vauthors = Chukkapalli SS, Rivera MF, Velsko IM, Lee JY, Chen H, Zheng D, Bhattacharyya I, Gangula PR, Lucas AR, Kesavalu L | display-authors = 6 | title = Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE(-/-) mice causally links periodontal disease and atherosclerosis | journal = Infection and Immunity | volume = 82 | issue = 5 | pages = 1959–67 | date = May 2014 | pmid = 24566627 | pmc = 3993427 | doi = 10.1128/IAI.01511-14 }}</ref>
* [https://www.ncbi.nlm.nih.gov/genome/?term=Treponema+denticola NCBI Genome Database: Treponema denticola]
 
* [https://www.cdc.gov/oralhealth/ CDC Oral Health]
=== Pancreatic Cancer ===
{{Bacteria}}
It has been recognised that there is an association between oral and intestinal cancer related deaths and chronic [[Periodontal disease|periodontitis]]. This is based on the high amounts of tumor suppressor gene p53 mutations and k-ras arginine mutations found in patients with pancreatic cancer. Peptidylarginine deiminases from oral bacteria are thought to be responsible for these mutations. This means that there could be a causative link between oral bacteria, particularly the red complex, and pancreatic cancer.<ref name=":0" />
[[Category:Treponema|denticola]]
 
[[Category:Periodontal pathogens]]
== See also ==
[[Category:Anaerobic bacteria]]
* [[Oral microbiology]]
[[Category:Gram-negative bacteria]]
* [[Periodontitis]]
{{nt}}
* [[List of bacterial vaginosis microbiota]]
 
== References ==
{{Reflist|30em}}
 
{{Gram-negative non-proteobacterial bacterial diseases}}
{{adapted}}
 
[[Category:Dentistry]]
[[Category:Spirochaetes]]
[[Category:Treponema]]
[[Category:Bacterial vaginosis]]
[[Category:Bacteria described in 1886]]
[[Category:Periodontal disorders]]

Latest revision as of 01:09, 5 January 2025

Treponema denticola is a Gram-negative anaerobic spirochete bacterium that is commonly found in the human oral cavity. It is one of the main pathogens associated with periodontal disease, a chronic inflammatory condition affecting the tissues surrounding the teeth.

Morphology[edit]

Treponema denticola is characterized by its unique helical shape, typical of spirochetes. It is a slender, tightly coiled bacterium, approximately 0.2 to 0.5 micrometers in diameter and 6 to 15 micrometers in length. The bacterium is motile, possessing endoflagella that run along the length of the cell, allowing it to move in a corkscrew motion.

Genomic Characteristics[edit]

The genome of Treponema denticola has been fully sequenced, revealing a circular chromosome of approximately 2.8 million base pairs. The genome encodes for a variety of proteins involved in metabolism, virulence, and motility. Notably, T. denticola possesses genes for proteolytic enzymes that degrade host tissues and immune evasion mechanisms.

Pathogenicity[edit]

Treponema denticola is a key component of the red complex, a group of bacteria strongly associated with periodontitis. It contributes to disease through several mechanisms:

Clinical Significance[edit]

Treponema denticola is implicated in the progression of periodontal disease, which can lead to tooth loss and has been associated with systemic conditions such as cardiovascular disease and diabetes mellitus. Detection of T. denticola in subgingival plaque is often used as a diagnostic marker for periodontal disease.

Diagnosis[edit]

Diagnosis of Treponema denticola infection is typically performed using:

  • Polymerase Chain Reaction (PCR): Highly sensitive and specific for detecting T. denticola DNA in clinical samples.
  • Microscopy: Dark-field or phase-contrast microscopy can visualize the spirochete's characteristic morphology.
  • Culture: Although challenging due to its fastidious nature, T. denticola can be cultured under anaerobic conditions.

Treatment[edit]

Management of infections involving Treponema denticola includes:

Research Directions[edit]

Ongoing research is focused on understanding the molecular mechanisms of Treponema denticola pathogenicity and its interactions with other oral microbiota. Novel therapeutic approaches, including vaccines and probiotics, are being explored to prevent and treat periodontal disease.

See Also[edit]

External Links[edit]