Characterization of Selenomonas sputigena pathogenesis

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Project Summary Selenomonas sputigena is a Gram-negative, flagellated, motile periodontal bacteria highly associated with periodontitis. S. sputigena is more prevalent and abundant in periodontitis gingival sites than in healthy gingiva. Selenomonas spp. are routinely isolated from periodontal samples, and gingival inflammation has long been associated with an increased abundance. Characterization of the human oral microbiome has highlighted that many bacteria, including S. sputigena, are associated with periodontitis. However, very little is known about the pathogenic capabilities of the organism. To that end, we recently initiated the first comprehensive study of S. sputigena pathogenesis and virulence properties. We demonstrated S. sputigena binds to gingival epithelial cells and promotes extensive pro-inflammatory cytokine secretion. Interestingly, we observed that S. sputigena evaded TLR5 activation, which recognizes flagellin. This is clinically important as our preliminary data demonstrate that motility and chemotaxis genes are highly expressed during periodontitis. Additionally, S. sputigena is densely packed within plaque biofilm, contributing to its structural organization, and interacts with other periodontal bacteria in polymicrobial communities. Finally, S. sputigena produces the secondary messenger c-di-GMP, which regulates motility and biofilm development. Our scientific premise is that motility and biofilm development are virulence factors that contribute to periodontal disease. Based on our preliminary data and the literature, we hypothesize that S. sputigena c-di-GMP regulates lifestyle decisions between motility and biofilm formation, impacting inflammation and pathogenicity. The aims of this study will test our hypothesis in two approaches: 1) we will determine c-di-GMP levels in biofilms, and during planktonic growth, while identifying the proteins that bind c-di-GMP and carry out effector functions and, 2) we will characterize the immune mediators, leukocyte infiltration and alveolar bone loss caused by S. sputigena in murine models of infection. Successful completion of this study will advance our understanding of a long-recognized but poorly understood periodontal pathogen. Current therapeutic strategies for periodontitis were developed based on a few well-characterized pathogenic bacteria. The involvement of under-studied bacteria, such as S. sputigena, in the initiation and progression of periodontitis, may lead to re-evaluating treatment approaches or uncovering novel strategies to prevent or treat periodontitis.