Bacteroides forsythus is a Gram-negative oral anaerobe implicated in the development of periodontal disease pathogenesis. Although, very little is known about the virulence factors of this organism, based on our recent in vitro and in vivo studies, a surface-associated 98-kDa protein (BspA) has been suggested as a virulence factor. The BspA protein contains homologous sequences belonging to the leucine-rich repeat motif family (LRR), and to motifs belonging to the immunoglobulin superfamily (Ig-SF). In vitro, the BspA protein binds to extracellular matrix components fibronectin and fibrinogen, and to epithelial cells, and induces release of proinflammtory cytokines from monocytic cells. Further, a mutant of B. forsythus defective in BspA expression constructed in our laboratory has been found to be significantly attenuated in its ability to bind to fibronectin, fibrinogen, and epithelial cells. The studies proposed here will address the hypotheses that LRRs and IgSF domains are critical for host cell interactions via binding to specific cellular receptors, and that the BspA protein plays important roles in pathogenesis via mediating bacterial colonization and triggering of host cellular responses, such as release of cytokines and other mediators. The experimental design will include: 1) studies to determine the specific BspA-domains involved in host cell (epithelial and monocytic cells) interactions (Specific Aim 1a), and investigate intracellular signaling events resulting from BspA binding (Aim 1b); 2) biochemical characterization of epithelial (Aim 2a) and monocyte receptors (Aim 2b) that bind BspA protein; and 3) assessment of the in vivo role of BspA protein as judged by studies in a mouse model of periodontal disease (Aim 3a), and by evaluating the host immune response against the BspA protein in patients with a history of periodontitis (Aim 3b). The findings will be important in determining the roles of BspA protein, and the underlying contribution of its domains in bacterial pathogenesis. The studies will also be critical from a proteomic standpoint in defining the roles of LRR and Ig-like signatures found in other bacterial proteins in general. In the long term, understanding the basic mechanisms of the BspA-mediated pathogenesis of B. forsythus will be vital in developing intervention strategies against periodontal disease.

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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Lunsford, Dwayne
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State University of New York at Buffalo
Schools of Dentistry
United States
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Ruscitto, A; Sharma, A (2018) Peptidoglycan synthesis in Tannerella forsythia: Scavenging is the modus operandi. Mol Oral Microbiol 33:125-132
Settem, R P; Honma, K; Shankar, M et al. (2018) Tannerella forsythia-produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes. Mol Oral Microbiol 33:292-299
Dong, Youyi; Zhang, Celia; Frye, Mitchell et al. (2018) Differential fates of tissue macrophages in the cochlea during postnatal development. Hear Res 365:110-126
Honma, Kiyonobu; Ruscitto, Angela; Sharma, Ashu (2017) ?-glucanase activity of the oral bacterium Tannerella forsythia contributes to the growth of a partner species, Fusobacterium nucleatum, in co-biofilms. Appl Environ Microbiol :
Chinthamani, Sreedevi; Settem, Rajendra P; Honma, Kiyonobu et al. (2017) Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. PLoS One 12:e0173394
Friedrich, Valentin; Janesch, Bettina; Windwarder, Markus et al. (2017) Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications. Glycobiology 27:342-357
Vinogradov, Evgeny; St Michael, Frank; Homma, Kiyonobu et al. (2017) Structure of the LPS O-chain from Fusobacterium nucleatum strain 10953, containing sialic acid. Carbohydr Res 440-441:38-42
Ruscitto, Angela; Hottmann, Isabel; Stafford, Graham P et al. (2016) Identification of a Novel N-Acetylmuramic Acid Transporter in Tannerella forsythia. J Bacteriol 198:3119-3125
Honma, Kiyonobu; Ruscitto, Angela; Frey, Andrew M et al. (2016) Sialic acid transporter NanT participates in Tannerella forsythia biofilm formation and survival on epithelial cells. Microb Pathog 94:12-20
Stafford, Graham P; Chaudhuri, Roy R; Haraszthy, Violet et al. (2016) Draft Genome Sequences of Three Clinical Isolates of Tannerella forsythia Isolated from Subgingival Plaque from Periodontitis Patients in the United States. Genome Announc 4:

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