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Regulatory Mechanisms Controlling P. gingivalis Surface Structures

Award Number: R01DE033659
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: 05/02/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Regulatory Mechanisms Controlling P. gingivalis Surface Structures - Porphyromonas gingivalis (Pg) is an endogenous pathogen, strongly implicated in the etiology of adult periodontal disease. This research will increase our understanding of the molecular mechanisms that control synthesis of Pg’s capsule and membrane lipids. Our overarching model is that the biofilm state acts as a reservoir of bacteria, while capsule synthesis is linked to a transition to virulence and disruption of homeostasis. We have shown that DNABII family members in Pg (HU PG0121 and HU PG1258) are involved in controlling production of capsule. In general, DNABII proteins are known to be critical for regulation of cell metabolism, the response to environmental perturbations, and in controlling the transition to and from a quiescent state. Central to our studies is an antisense RNA (asSuGR, for antisense Surface Glycan Regulator) encoded at the 5’-end of the capsule locus (PG0104-PG0121) within a novel 77bp inverted repeat (77bpIR) element. Deletion or over- expression of asSuGR alters the synthesis of both K- antigen capsule and LPS, and expression is, in part, controlled by the two-component response regulator PG0720. In addition, we have determined that synthesis of a certain subset of sphingolipids is required for the presentation of K-antigen capsule on the cell surface, and this finding aligns with our discovery of a matching asSuGR target sequence in a sphingolipid-synthesis locus (PG1780-PG1788). Our working model is that genes involved in K- antigen capsule and SL-synthesis are coordinately regulated by asSuGR. In these studies, we will determine how DNABII proteins along with other regulatory proteins and asSuGR modulate the synthesis of capsule, LPS, and sphingolipids and we will elucidate the ligand/signal that activates the two-component system (PG0719-PG0720). Our overall goal is to identify regulatory pathways that control the switch from a persistent, surface-attached state to a virulent state capable of disrupting microbe-host homeostasis. The research proposed in this application is significant because understanding the control of surface property changes is a vital link to understanding the switch this bacterium makes to a virulent pathogen. As an outcome of these studies, we will have characterized mechanisms that control the synthesis of key virulence determinants. This information will lead to a better understanding of the regulatory networks that either direct P. gingivalis to become a virulent pathogen or to continue to lie low and persist. Our results will potentially lead to the development of new therapeutic strategies for modulating biofilm growth and persistence of this oral pathogen.


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 = $598,960 )
2025	2025	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	2	5/9/2025	NON-COMPETING CONTINUATION	$59,894
2025	2025	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	2	3/19/2025	NON-COMPETING CONTINUATION	$539,066
														Subtotal = $598,960

Issue Date FY: 2024 ( Subtotal = $553,165 )
2024	2024	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	1	5/2/2024	NEW	$553,165
														Subtotal = $553,165

Grand Total All Awards = $1,152,125

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Regulatory Mechanisms Controlling P. gingivalis Surface Structures

Award Number: R01DE033659

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: 05/02/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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