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Mechanisms of Porphyromonas gingivalis sialoglycoproteases in virulence andhost interactions

Award Number: R03DE026526
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: 03/01/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2019

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Mechanisms of Porphyromonas gingivalis sialoglycoproteases in virulence andhost interactions - The microenvironment of the periodontal pocket contain an abundance of sialylated glycoproteins. P. gingivalis a key stone pathogen has been shown to enable the emergence of dysbiotic oral bacterial communities, hence play an important role in periodontal pathogenesis. They also express sialoglycorptoeases which break down the terminal sialic acids in the sialoglycoproteins. This breakdown contributes to many important biological functions by either exposing or masking the interacting receptors. Studies have shown the importance of these enzymes in virulence and pathogenesis of P. gingivalis and also in other bacteria. Our preliminary in vitro data showed the involvement of P. gingivalis sialoglycoproteases (PG-Sgps) (PG0778 & PG1724) in virulence modulation and show binding specificity to common glycoprotein subtypes found in eukaryotic cells. However, there is still a significant gap in knowledge of how PG-Sgps orchestrate host- pathogen interaction and virulence leading to dysbiosis. Our central hypothesis is that PG-Sgps are involved in virulence regulation and contribute to host interaction through surface glycan modifications of specific virulence glycoproteins and mediate immune evasion through interactions with cell surface sialylated ligands in neutrophils. We will test our hypothesis by completion of the following specific aims: (1). Identify the functional role of P. gingivalis sialoglycoproteases and surface glycan changes influencing pathogenic potential of the organism. (2).Study the in vivo virulence of P. gingivalis sialoglycoproteases and identify PG-Sgp mediated neutrophil interactions involved in dysregulation of innate immunity. This work will advance our understanding of P. gingivalis virulence and pathogenicity by studying the functional role of PG-Sgps through identification of specific glycan modification in two important virulence determinants of P. gingivalis. And to study, how PG-Sgps interact with neutrophils influencing the pathogenic potential of P. gingivalis. This will eventually lead us to expand our scope for understanding specific sialic acid ligand interactions and their role in immune evasion and subversion of P. gingivalis. This study will lead us to design potential therapeutic targets against the sialic acid specific ligands. Hence, will pave the way for future pharmacological prevention of P. gingivalis infection. .


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: 2020 ( Subtotal = -$158,676 )
2020	2018	LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION	25884 BUSINESS CENTER DR STE A	REDLANDS	CA	92374	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	3	5/3/2020	NON-COMPETING CONTINUATION	-$109,875
2020	2017	LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION	25884 BUSINESS CENTER DR STE A	REDLANDS	CA	92374	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	001	2	5/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$48,801
														Subtotal = -$158,676

Issue Date FY: 2018 ( Subtotal = $101,250 )
2018	2018	LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION	710 BROOKSIDE AVE STE 2	REDLANDS	CA	92373	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	002	3	9/11/2018	NON-COMPETING CONTINUATION	$109,875
2018	2017	LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION	710 BROOKSIDE AVE STE 2	REDLANDS	CA	92373	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	001	2	6/12/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$109,875
2018	2017	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	1	6/11/2018	NEW	-$118,500
														Subtotal = $101,250

Issue Date FY: 2017 ( Subtotal = $118,500 )
2017	2017	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	1	6/9/2017	NEW	$118,500
														Subtotal = $118,500

Grand Total All Awards = $61,074

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Mechanisms of Porphyromonas gingivalis sialoglycoproteases in virulence andhost interactions

Award Number: R03DE026526

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: 03/01/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2019

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