The OppA PEPTIDE Permease HOMOLOGUE OF ORAL SPIROCHETES

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Surface-associated proteins of Treponema denticola mediate interactions between the spirochete and sub-gingival tissues in periodontal diseases. Proteins having direct cytopathic effects have been a primary focus of research. However, very little is known of the mechanisms this peptidolytic and proteolytic organism must utilize for nutrient acquisition, and may utilize in specific signaling pathways or in evasion of host defenses. These processes can be key factors in the development of many infectious diseases. Molecular genetic studies of oral spirochetes are crucial to analysis of spirochete-host interactions in periodontal diseases and contribute to understanding infectious diseases caused by frankly pathogenic spirochetes. The present proposal explores the potential role of T. denticola OppA in periodontal pathogenesis. This protein, present in surface extracts of T. denticola, is encoded by a highly conserved genetic locus that includes oppA, -B, -C, -D and -F, the components of an ATP-binding cassette (ABC) transporter family involved in pep-tide nutrient uptake and trans- membrane environmental signaling in a wide range of bacteria. Preliminary studies showed that OppA bound soluble host proteins abundant in inflamed subgingival tissue. We hypothesize that OppA binding of host cell proteins contributes to the pathogenesis of organism by (i) accretion of host peptides or proteins to the spirochete surface, resulting in modulation or evasion of host responses; or (ii) peptide transport into the cell for use in metabolic or environmental signaling pathways. This proposal complements studies underway in this laboratory on assembly of membrane complexes comprised of outer membrane porins and proteases, and includes novel approaches to the study of the role of T. denticola in periodontal pathogenesis. Recombinant expression systems will be used to investigate the structure and function of OppA and to characterize its interaction with host extracellular matrix and serum components present in the subgingival environment. Molecular genetic analysis of this putative transport system will contribute to the understanding of bacterial interactions with host tissue components in periodontal diseases, as well as to basic knowledge of the biology of pathogenic spirochetes.