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Molecular signaling mechanisms of the periopathogen, Treponema denticola.

ABSTRACT: In the healthy subgingiva, oral treponemes account for a small percentage of the total bacteria. However, in diseased periodontal pockets, treponemes thrive and become a dominant component of the bacterial population. Oral treponemes are uniquely adept at capitalizing on the environmental conditions that develop with periodontal disease. The molecular basis of adaptive responses of oral treponemes is just beginning to be investigated and defined. The completion of several treponeme genome sequences and the characterization of global regulatory systems provide an important starting point in the analysis of signaling and adaptive responses. In this review, we discuss existing literature focused on the genetic regulatory mechanisms of Treponema denticola and present an overview of the possible roles of regulatory proteins identified through genome analyses. This information provides insight into the possible molecular mechanisms utilized by oral spirochetes to survive in the periodontal pocket and transition from a minor to a dominant organism.

SUBMITTER: Frederick JR

PROVIDER: S-EPMC3173007 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Molecular signaling mechanisms of the periopathogen, Treponema denticola.

Frederick J R JR Sarkar J J McDowell J V JV Marconi R T RT

Journal of dental research 20110329 10

In the healthy subgingiva, oral treponemes account for a small percentage of the total bacteria. However, in diseased periodontal pockets, treponemes thrive and become a dominant component of the bacterial population. Oral treponemes are uniquely adept at capitalizing on the environmental conditions that develop with periodontal disease. The molecular basis of adaptive responses of oral treponemes is just beginning to be investigated and defined. The completion of several treponeme genome sequen ...[more]

PMID: 21447698

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Project description:The oral spirochete Treponema denticola is a keystone periodontal pathogen that, in association with members of a complex polymicrobial oral biofilm, contributes to tissue damage and alveolar bone loss in periodontal disease. Virulence-associated behaviors attributed to T. denticola include disruption of the host cell extracellular matrix, tissue penetration and disruption of host cell membranes accompanied by dysregulation of host immunoregulatory factors. T. denticola dentilisin is associated with several of these behaviors. Dentilisin is an outer membrane-associated complex of acylated subtilisin-family PrtP protease and two other lipoproteins, PrcB and PrcA, that are unique to oral spirochetes. Dentilisin is encoded in a single operon consisting of prcB-prcA-prtP. We employ multiple approaches to study mechanisms of dentilisin assembly and PrtP protease activity. To determine the role of each protein in the protease complex, we have made targeted mutations throughout the protease locus, including polar and nonpolar mutations in each gene (prcB, prcA, prtP) and deletions of specific PrtP domains, including single base mutagenesis of key PrtP residues. These will facilitate distinguishing between host cell responses to dentilisin protease activity and its acyl groups. The boundaries of the divergent promoter region and the relationship between dentilisin and the adjacent iron transport operon are being resolved by incremental deletions in the sequence immediately 5' to the protease locus. Comparison of the predicted three-dimensional structure of PrtP to that of other subtilisin-like proteases shows a unique PrtP C-terminal domain of approximately 250 residues. A survey of global gene expression in the presence or absence of protease gene expression reveals potential links between dentilisin and iron uptake and homeostasis in T. denticola. Understanding the mechanisms of dentilisin transport, assembly and activity of this unique protease complex may lead to more effective prophylactic or therapeutic treatments for periodontal disease.

Dataset Information

Molecular signaling mechanisms of the periopathogen, Treponema denticola.

Publications

Molecular signaling mechanisms of the periopathogen, Treponema denticola.

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