This application will utilize biochemical and molecular genetic approaches to examine the virulence factors of the oral spirochete Treponema denticola. Since the motility of these organisms appears to be an important factor in the pathogenicity of the organisms, the mechanisms of chemotaxis in the spirochete will be investigated. Based upon the recent isolation in this laboratory of two T. denticola genes which are homologous to the methyl-accepting chemotaxis proteins of other bacteria, the respective roles of the two genes in motility will be examined. Mutants defective in each gene will be constructed utilizing a gene inactivation system recently developed in this laboratory and examined for defects in chemotaxis as well as in invasion through the extracellular matrix. Extracellular vesicle formation in gram-negative bacteria, including T. denticola, appears to play a role in invasiveness and nutrition of the organisms. However, little information is currently available concerning the molecular basis for the expression of the vesicles. Therefore, studies are proposed to examine the role of the stringent response in regulating the expression of vesicles in the oral spirochete. The role of the relA gene in this process will be investigated following isolation, characterization, and mutagenesis of the gene. Since a number of virulence-associated spirochetes cannot be readily cultivated in the laboratory, the recent development of a gene transfer system in T. denticola in this laboratory now makes it feasible to clone genes from the former organisms into the oral spirochete. In order to evaluate the potential for the construction of such model systems, selected genes from the syphilitic spirochete Treponema pallidum will be expressed in T. denticola. Such systems can serve as model systems for assessing the virulence potential of organisms which cannot be easily manipulated in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009821-10
Application #
6164406
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Mangan, Dennis F
Project Start
1992-02-20
Project End
2001-07-31
Budget Start
2000-02-20
Budget End
2001-07-31
Support Year
10
Fiscal Year
2000
Total Cost
$180,606
Indirect Cost
Name
State University of New York at Buffalo
Department
Dentistry
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
He, X; Lux, R; Kuramitsu, H K et al. (2009) Achieving probiotic effects via modulating oral microbial ecology. Adv Dent Res 21:53-6
Cameron, Caroline E; Kuroiwa, Janelle M Y; Yamada, Mitsunori et al. (2008) Heterologous expression of the Treponema pallidum laminin-binding adhesin Tp0751 in the culturable spirochete Treponema phagedenis. J Bacteriol 190:2565-71
Kuramitsu, Howard K; He, Xuesong; Lux, Renate et al. (2007) Interspecies interactions within oral microbial communities. Microbiol Mol Biol Rev 71:653-70
Kuramitsu, Howard K; Chen, Wen; Ikegami, Aki (2005) Biofilm formation by the periodontopathic bacteria Treponema denticola and Porphyromonas gingivalis. J Periodontol 76:2047-51
Han, Yiping W; Ikegami, Akihiko; Rajanna, Chythanya et al. (2005) Identification and characterization of a novel adhesin unique to oral fusobacteria. J Bacteriol 187:5330-40
Yamada, Mitsunori; Ikegami, Akihiko; Kuramitsu, Howard K (2005) Synergistic biofilm formation by Treponema denticola and Porphyromonas gingivalis. FEMS Microbiol Lett 250:271-7
Ishihara, Kazuyuki; Kuramitsu, Howard K; Okuda, Katsuji (2004) A 43-kDa protein of Treponema denticola is essential for dentilisin activity. FEMS Microbiol Lett 232:181-8
Ikegami, Akihiko; Honma, Kiyonobu; Sharma, Ashu et al. (2004) Multiple functions of the leucine-rich repeat protein LrrA of Treponema denticola. Infect Immun 72:4619-27
Chauhan, Sarita; Kuramitsu, Howard K (2004) Sequence analysis of plasmid pTS1 isolated from oral spirochetes. Plasmid 51:61-5
Vesey, Peter M; Kuramitsu, Howard K (2004) Genetic analysis of Treponema denticola ATCC 35405 biofilm formation. Microbiology 150:2401-7

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