|Year : 2016 | Volume
| Issue : 1 | Page : 58-62
Treponema denticola: A teammate in periodontal progression
Nymphea Pandit, Shalini Gugnani, Divya Sushil, Deepika Bali
Department of Periodontology and Oral Implantology, DAV (C) Dental College, Yamuna Nagar, Haryana, India
|Date of Web Publication||12-Feb-2016|
Dr. Divya Sushil
No. 1323, Sector - 3, Haryana Urban Development Authority, Rohtak - 124 001, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
There is compelling evidence that treponemes are involved in the etiology of several chronic oral diseases, including chronic periodontitis and other forms of periodontal disease. Treponema denticola suppresses fibroblast proliferation, enhancement of collagen phagocytosis by gingival fibroblasts, and the activation of both the classic and the alternative pathways of human complement. It was further shown to perturb actin regulating pathways in host cells. Recent advances, especially in molecular-based methodologies, have greatly improved our knowledge of this bacterium and its role in disease. An electronic and manual search based on agreed search phrases between the primary investigator and a secondary investigator was performed for the literature review until the year 2014. PubMed/MEDLINE databases were searched for studies to identify appropriate articles in relation to T. denticola and its virulence factors. The articles that were identified by this systematic review (total of 150) were analyzed in detail, which included the study of inference and conclusion. Within the limits of this systematic review, it can be concluded that T. denticola induces immune inflammatory response in periodontitis subjects. Procedures for gene inactivation provide a basis for characterizing the virulence factors of T. denticola, and thereby establishing its role as a teammate with other virulent plaque microorganisms in the process of tissue destruction.
Keywords: Chronic periodontitis, immunomodulation, lipooligosaccharide
|How to cite this article:|
Pandit N, Gugnani S, Sushil D, Bali D. Treponema denticola: A teammate in periodontal progression. J Int Clin Dent Res Organ 2016;8:58-62
|How to cite this URL:|
Pandit N, Gugnani S, Sushil D, Bali D. Treponema denticola: A teammate in periodontal progression. J Int Clin Dent Res Organ [serial online] 2016 [cited 2020 Jan 28];8:58-62. Available from: http://www.jicdro.org/text.asp?2016/8/1/58/176257
| Introduction|| |
Periodontal diseases result from interactions between periodontal microflora and multifaceted host response. Treponema denticola is frequently isolated from sites of severe infection in patients with periodontitis.  It suppresses fibroblast proliferation, enhancement of collagen phagocytosis by gingival fibroblasts, and the activation of both the classic and the alternative pathways of human complement, and their presence evidently exacerbates the damage to the supporting periodontal tissues.  In this article, we will concentrate on the virulence characteristics of oral treponemes, and particularly T. denticola, in relation to chronic periodontitis. When considering the virulence characteristics of T. denticola, it is imperative to understand that it is part of a pathogenic bacterial consortium, and its interactions with other bacterial species are important for disease pathology. 
| Virulence Factors|| |
Virulence is defined as the capacity of a pathogen, usually a microorganism, to cause disease. The potential virulence factors of this microorganism include: 
Major outer sheath protein (Msp)
Structure and Situation: Msp appears to be a ubiquitous outer sheath protein in oral treponemes, It is a β-barrel, integral outer sheath protein that acts as a porin and has surface-exposed loops that are able to bind to a variety of host proteins.
Role of Msp in adherence
It is a fibonectin and laminin binding protein involved in binding to fibroblasts. Binding of Msp occurred preferentially to the N-terminal heparin I/fibrin I domain of fibronectin. It was reported to be a candidate ligand for co-aggregation reactions between T. denticola and Porphyromonas gingivalis or Fusobacterium nucleatum.
Role of Msp in Immunomodulation
Msp activates innate immunity via Toll like receptor 2. Recent reports also indicated that T. denticola cells and Msp-induced innate immune responses of macrophages through Toll like receptor 2-myeloid differentiation factor 88 (MyD88). 
Role of Msp in cytotoxicity
Adherence of Msp disturbs calcium signalling in human fibroblasts by uncoupling store-operated channels. This may cause two potential pathological responses: An early, acute rise in intracellular calcium ion concentration due to increased conductance across the plasma membrane, and delayed perturbation of store-operated calcium flux. ,,
Ortholog of oligopeptide transporter unit
Structure and Situation: OppA is a 70-kDa cell-surface, membrane-associated lipoprotein that has significant similarity to the solute binding protein of a highly conserved ATP-binding cassette-type transporter involved in peptide uptake and environmental signalling in a wide range of bacteria.
Function: Oppa has been reported to bind to host proteins fibronectin and plasminogen in the subgingival environment. OppA did not bind to immobilized substrates or to epithelial cells, suggesting that this protein does not participate in direct adherence to cell-bound receptors. ,
Factor H-like protein-1 binding proteins
Structure and Situation: Factor H comprises a series of short consensus repeats consisting of approximately 50-60 residues. FhbB is a small (11.4 kDa) surface-exposed T. denticola lipoprotein that binds complement regulatory proteins of the factor H (FH) family. 
Function: It is involved in the down-regulation of C3b production. Adherence of microorganisms to these proteins has been demonstrated to facilitate evasion from alternative complement cascades and/or to play roles in the adherence to and invasion of host cell. ,,
Structure and Situation: It is an active cell-surface-located protease that cleaves at phenylalanyl/alanyl and prolyl/alanyl bonds. The active site of these serine proteases contains a His-Asp-Ser motif in chymotrypsin that is believed to be responsible for catalyzing the hydrolysis of peptide bonds. It contributes to disease progression by disrupting or modulating intercellular host signalling pathways and degrading host cell matrix proteins.
Role of dentilisin In adherence
Ligand for co-aggregation with P. gingivalis.
Coaggregation is a major strategy for colonization into dental plaque biofilms. It occurs via the adherence of cells to the surface of biofilms. T. denticola has been reported to co-aggregate with several members of dental plaque, such as P. gingivalis, Tanerella forsythia, and F. Nucleatum. ,,
Role of dentilisin in immunomodulation
Activation of complement pathway by cleaving C3.
Role of dentilisin in cytotoxicity
Dentilisin degrades the synthetic substrates prolylphenylalanine and prolyl-leucine. It also degrades natural substrates and attenuates the activation of complement via the degradation of C3b. This activation induced the release of matrix metalloproteinase-9 from polymorphonuclear cells, and matrix metalloproteinase-9 was reported to be involved in the progression of periodontitis. ,,
Leucine rich repeats
Structure and Situation: The leucine-rich repeat proteins are members of the CTD family of proteins that are secreted and attached to the cell surface by novel mechanism. Six Lrr proteins are predicted in the T. denticola genome. Leucine-rich repeats are protein-interaction motifs of 20-29 residues consisting of a high proportion of leucine residues.
Function: The major function of leucine-rich repeats is to to provide a structural framework for the formation of protein-protein interactions. LrrA is a T. denticola ATCC 35405 protein containing leucine-rich repeats. ,
Structure and Situation: Immunosuppressive factors have been reported in several oral microorganisms, including T. denticola. Fractions from T. denticola, with molecular mass values of approximately 100 and 50 kDa, respectively are located in the cytoplasm. ,
Function: The proteins inhibited the suppressed human peripheral mononuclear cells and fibroblasts progression of phytohemagglutinin- treated human peripheral blood mononuclear cells beyond the G1 phase through CD69 and CD25, which are associated with the transition through the G1 phase of the cell cycle. ,
Structure and Situation: The treponemal outer sheath does not have a typical Lipopolysaccharide. The treponeme outer sheath (membrane) contains lipooligosaccharides (LOS), Lipooligosaccharides (LOS) are glycolipids found in the outer membrane of Gram negative bacteria. It consists of two regions Lipid A and R Polysaccharide (core glycolipid), and lacks O antigen.
Role of lipooligosaccharide in immunomodulation
The lipooligosaccharide of Treponema denticola up-regulated the receptor activator of nuclear factor kappa β and down-regulated osteoprotegerin. It also secretes pro-inflammatory cytokines, including IL-1, IL-6, IL-8, tumor necrosis factor (TNF), and platelet-activating factor. These, in turn, stimulate production of prostaglandins and leukotrienes. ,
Resistance to defensins
Role of defensins in immunomodulation
Antibacterial peptides play an important role in the initial host defense against microbial attack. These small cationic peptides interact with negatively charged cell wall components of bacteria and fungi disrupting membrane integrity. T. denticola is resistant to human beta defensins 1 and 2. In addition, a proton motive force inhibitor, carbonyl cyanide 3-chlorophenylhydrazone, increased the susceptibility of T. denticola to killing by human beta-defensin-3, suggesting a potential role for efflux pumps in resistance to this peptide. ,
Structure and Situation: Cystalysin is a 46 kDa pyridoxal 5′-phosphate (PLP) protein found in cytoplasm. It is a hemolytic protein capable of hemoxidizing haemoglobin and causing lyses of human erythrocytes.
Role of cystalysin in cytotoxicity
Cystalysin lyses erythrocytes, hemoxidized haemoglobin to sulfhemoglobin and methemoglobin, and removed the sulfhydryl and amino group from selected S-containing compounds (e.g. cysteine) producing H 2 S, NH 3 , and pyruvate. The addition of cystalysin to human periodontal ligament cells induce apoptosis and among the products of the metabolism of cysteine only hydrogen sulphide induces apoptosis of human cells. The central role of cystalysin in iron acquisition is further supported by the observation that cystalysin synthesis is significantly increased under conditions of iron deprivation. ,
Structure and Situation: The treponemes are unique in that their flagella located within the periplasm and, hence, are referred to as periplasmic flagella (PF). Each PF is subterminally attached to only one end of the cell cylinder and extends toward the opposite end. T. denticola has two PFs at each end that are long enough to overlap in the center of the cell.
Motility of the treponema
Motility is now widely recognized as a virulence factor for many pathogenic organisms. Movement of motile organisms is usually guided by a sophisticated chemotaxis system. Appendages for motility include- cilia and flagella. The flagellar filament of T. denticola consists of 3core proteins:
They are thought to be related to motility and the environmental-sensing functions of T. denticola. Treponemes achieve high densities when attached to cells and tissues. ,
The motility of T. denticola is dependent upon genes coding for periplasmic flagella and chemotaxis. Extracellular stimuli are sensed by membrane-spanning methyl-accepting chemotaxis proteins (Mcps). The signals are transformed into appropriate motor responses by the two-component system, CheA /Y. The stimulus is communicated to the motor via phosphotransfer reactions from CheA to the response regulator CheY, which controls the direction of flagellar motor rotation according to its phosphorylation level. Repellents increase the autophosphorylation of CheA, whereas attractants decrease this activity. They are a gene cluster responsible for this property in T. denticola. ,
Acquisition of metal
Hemin binding protein
Structure and Situation: Lactoferrin-binding proteins of 50 and 35 kDa, and heminbinding proteins of 47 and 44 kDa, were reported in T. denticola in the cytoplasm.
Function: The ability of potential pathogens to acquire iron in a host is an important determinant of both their virulence and the nature of the infection produced. Virulent gram-negative bacteria are capable of acquiring sufficient iron from the host because their virulence is unaffected by exogenous iron Acquisition of the Fe ion is essential for the growth of microorganisms. However, to date, few reports have characterized such systems in treponemes. Lactoferrin-binding proteins of 50 and 35 kDa, and hemin binding proteins of 47 and 44 kDa, were reported in T. denticola. 
| Conclusion|| |
The characteristics of T. denticola that represent its major virulence factors in chronic periodontitis are: Its motility and chemotaxis, which enable the bacterium to rapidly colonize new sites, penetrate deep periodontal pockets, and penetrate epithelial layers; its ability to interact synergistically with other periodontal pathogens on several levels; and its ability to produce cytotoxic metabolites. These are the specific properties that establish its role as a teammate with other virulent plaque microorganisms in the process of tissue destruction.
Recent analysis of T. denticola using molecular genetic techniques has begun to reveal the molecular basis for the physiology and pathogenicity of this microorganism. The analyses of cell signalling induced by this microorganism may help to explain their effects on host cell dynamics and hence further detailed analysis regarding the receptors and cascades of cell signalling induced by Treponema denticola is needed.
| References|| |
Holt SC, Ebersole JL. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia
: The "red complex", a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000 2005;38:72-122.
O′Brien-Simpson NM, Veith PD, Dashper SG, Reynolds EC. Antigens of bacteria associated with periodontitis. Periodontol 2000 2004;35:101-34.
Miao D, Godovikova V, Qian X, Seshadrinathan S, Kapila YL, Fenno JC. Treponema denticola
upregulates MMP-2 activation in periodontal ligament cells: Interplay between epigenetics and periodontal infection. Arch Oral Biol 2014;59:1056-64.
Ellen RP, Galimanas VB. Spirochetes at the forefront of periodontal infections. Periodontol 2000 2005;38:13-32.
Fenno JC. Treponema denticola
interactions with host proteins. J Oral Microbiol 2012;4:1-28.
Dashper SG, Seers CA, Tan KH, Reynolds EC. Virulence factors of oral spirochetes Treponema Denticola
. J Dent Res 2011;90:691-703.
Guo W, Kan JT, Cheng ZY, Chen JF, Shen YQ, Xu J, et al
. Hydrogen Sulfide as an endogenous modulator in mitochondria and mitochondria dysfunction. Oxid Med Cell Longev 2012; 2012:878052.
Ishihara K. Virulence factors of Treponema denticola.
Periodontol 2000 2010;54:117-35.
Tomich M, Planet PJ, Figurski DH. The tad locus: Postcards from the widespread colonization island. Nat Rev Microbiol 2007; 5:363-75.
Edwards AM, Jenkinson HF, Woodward MJ, Dymock D. Binding properties and adhesion-mediating regions of the major sheath protein of Treponema denticola
ATCC 35405. Infect Immun 2005;73:2891-8.
Rosen G, Genzler T, Sela MN. Coaggregation of Treponema denticola
with Porphyromonas gingivalis
and Fusobacterium nucleatum
is mediated by the major outer sheath protein of Treponema denticola
. FEMS Microbiol Lett 2008;289:59-66.
Amin M, Ho AC, Lin JY, Batista da Silva AP, Glogauer M, Ellen RP. Induction of de novo
subcortical actin filament assembly by Treponema denticola
major outer sheath protein. Infect Immun 2004;72:3650-4.
Puthengady Thomas B, Sun CX, Bajenova E, Ellen RP, Glogauer M. Modulation of human neutrophil functions in vitro
by Treponema denticola
major outer sheath protein. Infect Immun 2006;74:1954-7.
Tan KH, Seers CA, Dashper SG, Mitchell HL, Pyke JS, Meuric V, et al
. Porphyromonas gingivalis
and Treponema denticola
exhibit metabolic symbioses. PLoS Pathog 2014;10:e1003955.
Batista da Silva AP, Lee W, Bajenova E, McCulloch CA, Ellen RP. The major outer sheath protein of Treponema denticola
inhibits the binding step of collagen phagocytosis in fibroblasts. Cell Microbiol 2004;6:485-98.
Jobin MC, Virdee I, McCulloch CA, Ellen RP. Activation of MAPK in fibroblasts by Treponema denticola
major outer sheath protein. Biochem Biophys Res Commun 2007;356:213-8.
Sarkar J, McHardy IH, Simanian EJ, Shi W, Lux R. Transcriptional responses of Treponema denticola
to other oral bacterial species. PLoS One 2014;9:e88361.
Fenno JC, Tamura M, Hannam PM, Wong GW, Chan RA, McBride BC. Identification of a Treponema denticola
OppA homologue that binds host proteins present in the subgingival environment. Infect Immun 2000;68:1884-92.
Murphy K, Travers P, Walport M. Janeway′s Immunobiology. Garland Science. New York. 2008;2:1-10.
Józsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol 2008;29:380-7.
McDowell JV, Lankford J, Stamm L, Sadlon T, Gordon DL, Marconi RT. Demonstration of factor H-like protein 1binding to Treponema denticola, a pathogen associated with periodontal disease in humans. Infect Immun 2005;73:7126-32.
Alitalo A, Meri T, Chen T, Lankinen H, Cheng ZZ, Jokiranta TS, et al
. Lysine-dependent multipoint binding of the Borrelia burgdorferi virulence factor outer surface protein E to the C terminus of factor H. J Immunol 2004;172:95-101.
Hovis KM, Jones JP, Sadlon T, Raval G, Gordon DL, Marconi RT. Molecular analyses of the interaction of Borrelia hermsii FhbA with the complement regulatory proteins factor H and factor H-like protein 1. Infect Immun 2006;74:2007-14.
McDowell JV, Wolfgang J, Senty L, Sundy CM, Noto MJ, Marconi RT. Demonstration of the involvement of outer surface protein E coiled coil structural domains and higher order structural elements in the binding of infection-induced antibody and the complement-regulatory protein, factor H. J Immunol 2004;173:7471-80.
McDowell JV, Huang B, Fenno JC, Marconi RT. Analysis of a unique interaction between the complement regulatory protein factor H and the periodontal pathogen Treponema denticola
. Infect Immun 2009;77:1417-25.
Trouw LA, Bengtsson AA, Gelderman KA, Dahlbäck B, Sturfelt G, Blom AM. C4b-binding protein and factor H compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack. J Biol Chem 2007;282:28540-8.
Yamazaki T, Miyamoto M, Yamada S, Okuda K, Ishihara K. Surface protease of Treponema denticola
hydrolyzes C3 and influences function of polymorphonuclear leukocytes. Microbes Infect 2006;8:1758-63.
Miyamoto M, Ishihara K, Okuda K. The Treponema denticola
surface protease dentilisin degrades interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha. Infect Immun 2006; 74:2462-7.
Kumar MS, Vamsi G, Sripriya R, Sehgal PK. Expression of matrix metalloproteinases (MMP-8 and -9) in chronic periodontitis patients with and without diabetes mellitus. J Periodontol 2006;77:1803-8.
Ikegami A, Honma K, Sharma A, Kuramitsu HK. Multiple functions of the leucine-rich repeat protein LrrA of Treponema denticola
. Infect Immun 2004;72:4619-27.
Marttila E, Järvensivu A, Sorsa T, Grenier D, Richardson M, Kari K, et al
. Intracellular localization of Treponema denticola chymotrypsin-like proteinase in chronic periodontitis. J Oral Microbiol 2014;6:1-5.