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Impact of Saccharibacteria and their bacterial hosts in Periodontal and Inflammatory Diseases

Award Number: R01DE031274
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Human oral polymicrobial communities play a significant role in health and disease. Periodontitis is a polymicrobial disease and is among the most common infections of humans. Recent next-generation sequencing studies reveal that periodontal polymicrobial communities are comprised of a large diversity of bacterial species; however, we have little to no understanding of the disease-role of some of the key members. Saccharibacteria (TM7) is one such bacterial group that has been linked to multiple inflammatory diseases, including periodontitis. In addition, TM7 belongs to a major bacterial lineage termed Candidate Phyla Radiation. Candidate Phyla Radiation encompasses one-quarter of all bacterial diversity, yet they have been recalcitrant to laboratory cultivation. Oral TM7 bacteria were the first to be cultivated, opening the door to many intriguing questions due to their unique characteristics. TM7 has an ultra-small cell size (200-500 nm) with a highly reduced genome lacking essential biological functions. More importantly, it is an epiparasitic bacteria that grows on the surface of Actinobacteria (i.e., Actinomyces, Pseudopropionibacterium), which is another understudied bacterial group in humans. Actinomyces has been shown to induce inflammatory response both in cultured cells and in animal models. Our preliminary mouse periodontal studies were designed to investigate the role of TM7 and its host bacteria, Actinomyces, in vivo. TM7/host bacteria pairs induced less inflammatory bone loss compared to host bacteria alone, suggesting that oral Actinomyces and related bacteria can be a pathobiont (opportunistic pathogen), and their pathogenicity is regulated by TM7 bacteria. The current proposal will investigate pathogenic genes in TM7 host bacteria and how they are regulated by TM7 bacteria via metatranscriptomics. Identified genes will be further tested by site-directed mutagenesis in the host bacteria (Aim 1). The proposal will also determine the pathogenic and immunostimulatory activity of TM7 bacteria in epithelial and immune cell interaction assay and will identify TM7 macromolecules that are involved in their interaction with the eukaryotic cells (Aim 2). Lastly, this study will expand to culturing and characterizing additional taxonomically diverse TM7 bacteria from the periodontal patients, effectively creating a library of TM7 bacteria. This will allow us to determine the general immunological behavior of TM7/host bacteria across different TM7 species (Aim 3). Accomplishment of the proposal aims will improve the currently limited understanding of TM7 bacteria and its interaction with the host bacteria, as well as generate the first understanding of TM7's role in periodontal and inflammatory diseases.


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: 2024 ( Subtotal = $440,063 )
2024	2024	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	3	12/20/2023	NON-COMPETING CONTINUATION	$440,063
														Subtotal = $440,063

Issue Date FY: 2023 ( Subtotal = $521,771 )
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	2	12/14/2022	NON-COMPETING CONTINUATION	$469,594
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	2	2/13/2023	NON-COMPETING CONTINUATION	$52,177
														Subtotal = $521,771

Issue Date FY: 2022 ( Subtotal = $557,933 )
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	1	12/15/2021	NEW	$557,933
														Subtotal = $557,933

Grand Total All Awards = $1,519,767

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Impact of Saccharibacteria and their bacterial hosts in Periodontal and Inflammatory Diseases

Award Number: R01DE031274

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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