Friday, July 4, 2025 7/4/2025

L-Arg availability affects the physiological state of porphyromonas gingivalis.

Award Number: R01DE024580
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: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

Group Awards By:

View Award Description

L-Arg availability affects the physiological state of porphyromonas gingivalis. - Project Summary/Abstract Many chronic inflammatory diseases, including periodontal infections, are biofilm-based pathologies mediated by indigenous microbiota persisting within complex host-associated microbial communities. Determining the environmental cues that direct the physiological state (commensal versus pathogenic state) of oral anaerobes, is fundamental to development of therapeutic strategies for periodontal diseases. Recent studies indicate that the pathogenic potential of the anaerobic bacterium Porphyromonas gingivalis is not solely dependent on its ability to colonize and proliferate within the subgingival biofilm; its physiological state and its associations within the microbial consortium are fundamental to development of pathology. The central hypothesis for this application is that the availability of L-arginine is a key signal/substrate that impacts P. gingivalis surface translocation, expression of virulence determinants, and biofilm formation. Studies have reported that the levels of arginine increase 2-fold (from ~5µM to 10µM) in gingival crevicular fluid during periodontal disease. The reason for this increase is not known but may reflect a decrease in metabolism by the microbial community, a decrease in uptake by host cells, or an increase in bacterial arginine biosynthesis. One known factor is the activity of the arginine - specific cysteine proteases (Arg-gingipains) produced by P. gingivalis, along with its carboxypeptidase that releases the terminal arginine residues from peptides produced by Arg- gingipains. Our analysis shows that both intracellular and extracellular accumulation of L-arginine has a negative impact on P. gingivalis physiology, confirming that the levels of L-arginine are monitored and controlled. Our studies have shown that under L-arginine deplete conditions, P. gingivalis down regulates expression of fimbriae, inhibiting biofilm formation; and, in contrast, addition of L-arginine boosts fimbrial expression and surface colonization. Thus, P. gingivalis adjusts its lifestyle in response to changes in extracellular L-arginine. What remains unclear is the sensing and regulatory mechanisms that control this change in physiology. The goal of this application is to determine how P. gingivalis controls extracellular and intracellular arginine concentrations and in particular the effect of changes in arginine concentration on its ability to surface translocate. Importantly, L-arginine is known to be an important modulator of the host immune response to pathogens, so we posit that there is a delicate balance between host and pathogen responses to arginine during disease progression and that P. gingivalis has evolved with the ability to sense and respond to this key amino acid as a fundamental strategy for persistence. The rationale for these studies is that identifying the signals that control colonization and the physiological state of oral pathogens will provide prime targets for the development of therapeutic strategies. Thus, the long-term objective is to determine if this mechanism of signaling can be targeted for treatment and prevention of biofilm-induced diseases in humans.


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 = $393,590 )
2024	2024	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	10	6/28/2024	NON-COMPETING CONTINUATION	$393,590
														Subtotal = $393,590

Issue Date FY: 2023 ( Subtotal = $518,503 )
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	002	9	6/26/2023	NON-COMPETING CONTINUATION	$409,170
2023	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	004	8	6/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$122,536
2023	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	8	12/2/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$467,899
2023	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	7	12/1/2022	NON-COMPETING CONTINUATION	-$358,566
2023	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	003	6	6/27/2023	COMPETING CONTINUATION	-$122,536
														Subtotal = $518,503

Issue Date FY: 2022 ( Subtotal = $358,566 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	002	7	6/16/2022	NON-COMPETING CONTINUATION	$358,566
2022	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	6	12/3/2021	COMPETING CONTINUATION	$13,517
2022	2019	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	5	12/3/2021	NON-COMPETING CONTINUATION	-$13,517
														Subtotal = $358,566

Issue Date FY: 2021 ( Subtotal = $362,188 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	002	6	6/24/2021	COMPETING CONTINUATION	$362,188
2021	2019	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	5	3/9/2021	NON-COMPETING CONTINUATION	$0
2021	2019	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	5	6/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $362,188

Issue Date FY: 2019 ( Subtotal = $375,000 )
2019	2019	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	5	3/6/2019	NON-COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2018 ( Subtotal = $375,000 )
2018	2018	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	4	4/2/2018	NON-COMPETING CONTINUATION	$337,500
2018	2018	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	4	4/26/2018	NON-COMPETING CONTINUATION	$37,500
														Subtotal = $375,000

Issue Date FY: 2017 ( Subtotal = $375,000 )
2017	2017	UNIVERSITY OF FLORIDA	207 GRINTER HALL	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	3	2/16/2017	NON-COMPETING CONTINUATION	$337,500
2017	2017	UNIVERSITY OF FLORIDA	207 GRINTER HALL	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	3	5/26/2017	NON-COMPETING CONTINUATION	$37,500
														Subtotal = $375,000

Issue Date FY: 2016 ( Subtotal = $375,000 )
2016	2016	UNIVERSITY OF FLORIDA	PO BOX 113001, 302 TIGERT HALL	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	2	2/23/2016	NON-COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2015 ( Subtotal = $375,000 )
2015	2015	UNIVERSITY OF FLORIDA	PO BOX 113001, 302 TIGERT HALL	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	1	2/9/2015	NEW	$375,000
														Subtotal = $375,000

Grand Total All Awards = $3,507,847

Top

All Categories

About

Search

Reports

Data Submission

Award Information

L-Arg availability affects the physiological state of porphyromonas gingivalis.

Award Number: R01DE024580

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: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer