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Functional Characterizations of Phospholipase A2 in Porphyromonas gingivalis

Award Number: R01DE035482
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Functional Characterizations of Phospholipase A2 in Porphyromonas gingivalis - Project Summary Phospholipases (PLAs) are enzymes that hydrolyze phospholipids to produce fatty acids and lipophilic substances. These ubiquitous and diverse enzymes play critical roles in maintaining cell membrane integrity, lipid signaling, and energy homeostasis regulation. The metabolites of PLAs, such as prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), are potent inflammatory mediators and implicated in numerous human diseases, including atherosclerosis, Alzheimer's disease, and cancer. Periodontitis is a prevalent inflammatory disease that affects nearly half of American adults. Accumulating evidence demonstrates a positive correlation between PLA activity and periodontitis severity: the levels of PLA and its metabolites (e.g., PGE2 and LTB4) are significantly elevated in gingival crevicular fluid (GCF) from periodontitis patients and return to normal levels following treatment. However, the underlying pathogenic mechanisms driving this association remain poorly understood. Emerging evidence points to a potential bacterial contribution to this phenomenon. Porphyromonas gingivalis (Pg), a keystone periodontal pathogen, stimulates host PLA2 (a superfamily of PLAs) production in oral epithelial cells. Building on this observation, we interrogated Pg genomes and identified two PLA2 homologs in all sequenced Pg isolates (e.g., PG0898 and PG1879 in strain W83). Sequence analyses reveal that these homologs contain a conserved patatin-like phospholipase A2 domain present in several bacterial virulence factors such as ExoU, a key virulence determinant of Pseudomonas aeruginosa. Intriguingly, similar PLA2 homologs are present in other major oral pathobionts (Treponema denticola and Tannerella forsythia) but absent in oral commensals, suggesting that bacterial PLA2s may be a conserved virulence determinant among periodontal pathogens. However, these PLA2 homologs have not been functionally characterized in oral pathogens and their roles in periodontitis pathogenesis remain unexplored. This project seeks to address this critical knowledge gap using Pg as a model organism, focused on three integrated specific aims: (1) elucidate the biochemical and structural features of PG0898 and PG1879 and their catalytic mechanism as PLA2 enzymes; (2) investigate how these two PLA2 enzymes influence Pg physiology; and (3) decipher their roles in Pg virulence using integrated in vitro and in vivo approaches. This project is significant and innovative as it represents the first study to investigate the role of bacterial PLA2s in periodontitis pathogenesis. Completion of this work will elucidate the biochemical and structural features of PG0898 and PG1879 and their roles in Pg pathophysiology, establish a foundation for investigating PLA2 enzymes in other oral pathogens and their implications in periodontitis pathogenesis, and potentially lead to the development of novel therapeutic modalities (e.g., PLA2 inhibitors) for treating and preventing 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: 2026 ( Subtotal = $473,186 )
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Oral Diseases and Disorders Research	000	1	9/1/2026	NEW	$473,186
														Subtotal = $473,186

Grand Total All Awards = $473,186

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Functional Characterizations of Phospholipase A2 in Porphyromonas gingivalis

Award Number: R01DE035482

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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