There is a growing awareness that oral treponemes play a role in the progression from health to periodontitis. Despite the interest in the relationship of this genus to periodontitis, only a few Treponema spp. have been isolated and grown. Substantial literature has implicated Treponema denticola as an oral pathogen: however, few investigations have examined other species. These investigators have discovered that the predominant cultivable oral spirochete in subgingival These investigators propose to investigate T. pectinovorum virulence components and its potential contribution to the tissue and cellular destruction observed vitro and in vivo models which have been developed during the initial phases of the grant. The hypothesis to be tested is that T. pectinovorum is a major this organism presents unique outer membrane proteins and an LPS-like molecule distinctive from other oral treponemes, the hypothesis to be tested is that the 42 kDa major outer membrane protein (MompA) and the LPS like molecule (LPSL) have characteristics of virulence components in in vitro and in vivo models of disease. Successful testing of these hypotheses would imply that T. pectinovorum utilizes these components in subgingival plaque ecology to contribute to the soft tissue destructive and bone resorptive manifestations of functions of the 42 kDa major outer membrane protein (MompA) of T. pectinovorum including i) cloning and sequencing the MompA gene, ii) developing Abs to localize the molecule and determine its distribution among T. pectinovorum isolates, and iii) determining functional characteristics of MompA including its role as an adhesin for epithelial cells and fibroblasts, its activity as a ligand in eliciting host cell cytokine responses, and determination of its antigens capacity in a murine model. A highly innovative aspect of these studies will investigate variations in binding and effects on host cell functions following interaction of T. pectinovorum with fibroblasts derived from normal and HIV-infected individuals; 2) To isolate and characterize the LPSL molecule from T. pectinovorum including: i) biochemical characterization of the LPSL, ii) determining the endotoxic activity in vitro and in vivo, and iii) examining its biological functions in vitro and in vivo; and 3) To evaluate the presence and level of T. pectinovorum in human plaque samples using molecular and immunologic probes, including i) species-specific probes for T. pectinovorum and other oral treponemes, ii)MompA probes: iii) intragenic probes for T. pectinovorum; iv) Antibody to the MompA, and v) Ab to the LPSL.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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Nokta, Mostafa A
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University of Kentucky
Schools of Dentistry
United States
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Holt, Stanley C; Ebersole, Jeffrey L (2005) Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the ""red complex"", a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000 38:72-122
Kesavalu, L; Holt, S C; Ebersole, J L (2003) In vitro environmental regulation of Porphyromonas gingivalis growth and virulence. Oral Microbiol Immunol 18:226-33
Kesavalu, L; Chandrasekar, B; Ebersole, J L (2002) In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 17:177-80
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Xu, X; Holt, S C; Kolodrubetz, D (2001) Cloning and expression of two novel hemin binding protein genes from Treponema denticola. Infect Immun 69:4465-72
Nixon, C S; Steffen, M J; Ebersole, J L (2000) Cytokine responses to treponema pectinovorum and treponema denticola in human gingival fibroblasts. Infect Immun 68:5284-92
Chu, L; Ebersole, J L; Kurzban, G P et al. (1999) Cystalysin, a 46-kDa L-cysteine desulfhydrase from Treponema denticola: biochemical and biophysical characterization. Clin Infect Dis 28:442-50
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