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Characterization of Selenomonas sputigena pathogenesis

Award Number: R03DE032411
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/11/2023
PERIOD OF PERFORMANCE END DATE: 09/10/2026

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Characterization of Selenomonas sputigena pathogenesis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Oral Diseases and Disorders Research	000	1	8/27/2025	NEW	$0
2025	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Oral Diseases and Disorders Research	001	1	8/29/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Oral Diseases and Disorders Research	000	1	10/12/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $301,350 )
2023	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Oral Diseases and Disorders Research	000	1	9/8/2023	NEW	$301,350
														Subtotal = $301,350

Grand Total All Awards = $301,350

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Characterization of Selenomonas sputigena pathogenesis

Award Number: R03DE032411

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/11/2023

PERIOD OF PERFORMANCE END DATE: 09/10/2026

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