Highly Conserved Surface Proteins of Oral Spirochetes as Adhesins and Potent Inducers of Proinflammatory and Osteoclastogenic Factors

• Published in: Infection and Immunity Vol. 76; no. 6; pp. 2428 - 2438
• Main Authors: Jun, Hye-Kyoung, Kang, Young-Mi, Lee, Hae-Ri, Lee, Sung-Hoon, Choi, Bong-Kyu
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.06.2008; American Society for Microbiology (ASM)
• Subjects: Adhesins, Bacterial - genetics; Adhesins, Bacterial - immunology; Adhesins, Bacterial - metabolism; Amino Acid Sequence; Antibodies, Bacterial - immunology; Antigens, Surface - chemistry; Antigens, Surface - genetics; Antigens, Surface - immunology; Antigens, Surface - metabolism; Bacterial Infections; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Cell Line; Cloning, Molecular; Conserved Sequence; Epithelial Cells - metabolism; Escherichia coli; Gene Expression Regulation, Bacterial; Humans; Immunoglobulin G - immunology; Inflammation - metabolism; Molecular Sequence Data; Osteoclasts - metabolism; Protein Binding; Treponema; Treponema - genetics; Treponema - metabolism; Treponema denticola; Treponema pallidum; Up-Regulation
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01128-07

Oral spirochetes include enormously heterogeneous Treponema species, and some have been implicated in the etiology of periodontitis. In this study, we characterized highly conserved surface proteins in four representative oral spirochetes (Treponema denticola, T. lecithinolyticum, T. maltophilum, and T. socranskii subsp. socranskii) that are homologs of T. pallidum Tp92, with opsonophagocytic potential and protective capacity against syphilis. Tp92 homologs of oral spirochetes had predicted signal peptides (20 to 31 amino acids) and molecular masses of 88 to 92 kDa for mature proteins. They showed amino acid sequence identities of 37.9 to 49.3% and similarities of 54.5 to 66.9% to Tp92. The sequence identities and similarities of Tp92 homologs of oral treponemes to one another were 41.6 to 71.6% and 59.9 to 85.6%, respectively. The tp92 gene homologs were successfully expressed in Escherichia coli, and the recombinant proteins were capable of binding to KB cells, an epithelial cell line, and inhibited the binding of the whole bacteria to the cells. Antiserum (the immunoglobulin G fraction) raised against a recombinant form of the T. denticola Tp92 homolog cross-reacted with homologs from three other species of treponemes. The Tp92 homologs stimulated various factors involved in inflammation and osteoclastogenesis, like interleukin-1β (IL-1β), tumor necrosis factor alpha, IL-6, prostaglandin E₂, and matrix metalloproteinase 9, in host cells like monocytes and fibroblasts. Our results demonstrate that Tp92 homologs of oral spirochetes are highly conserved and may play an important role in cell attachment, inflammation, and tissue destruction. The coexistence of various Treponema species in a single periodontal pocket and, therefore, the accumulation of multiple Tp92 homologs may amplify the pathological effect in periodontitis.