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Folate-Modulated Virulence of Porphyromonas gingivalis

Award Number: F32DE031493
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 09/29/2024

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Folate-Modulated Virulence of Porphyromonas gingivalis - Periodontal disease, one of the most common infections of humans, is driven by pathogens that influence the composition and trajectory of the oral polymicrobial community. These pathogens can take hold in an inhospitable environment and pave the way for other organism to colonize and grow. A key factor in allowing a pathogen to establish itself and colonize despite these odds is successfully regulating the expression of virulence factors while acquiring enough essential nutrition for replication and growth. One such essential nutrient is folate, which is classically linked to modulation of virulence in microbes. Although the literature has shown that limiting folate availability leads to decreased virulence in many microbes, however, we have found a clear exception to this rule in the periodontal pathogen P. gingivalis, an asaccharolytic organism that uses an amino-acid based metabolism. As a model for studying how folate availability regulates virulence in asaccharolytic pathogens, we are investigating how restricting the ability of P. gingivalis to produce folate regulates its expression of virulence factors. The objectives of this study are to: i) define the metabolic phenotype of P. gingivalis induced by folate deficiency; ii) determine how the metabolic phenotype of P. gingivalis is associated with the expression of virulence factors; and iii) characterize the host immune response to folate-deficient P. gingivalis. The completion of this study will provide critical insight into how limiting folate availability does not universally suppress the virulence of pathogens, but has the potential to result in enhanced virulence in asaccharolytic pathogens. We will also provide novel information on how the flux of metabolites in the folate and one-carbon metabolic pathways are associated with virulence in P. gingivalis and how this could apply to other organisms utilizing non-carbohydrate based metabolisms. Our overall long-term goal is to apply these findings to refine when it is appropriate to use antifolates to treat microbial infections and reduce overall harm caused to patients. Further, these findings will help narrow down alternative pathways to target treatments for infections caused by asaccharolytic pathogens.


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: 2023 ( Subtotal = $72,592 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	3	8/25/2023	NON-COMPETING CONTINUATION	$72,592
														Subtotal = $72,592

Issue Date FY: 2022 ( Subtotal = $68,382 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	2	8/23/2022	NON-COMPETING CONTINUATION	$68,382
														Subtotal = $68,382

Issue Date FY: 2021 ( Subtotal = $66,794 )
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	1	9/3/2021	NEW	$66,794
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	1	9/3/2021	NEW	$0
														Subtotal = $66,794

Grand Total All Awards = $207,768

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Folate-Modulated Virulence of Porphyromonas gingivalis

Award Number: F32DE031493

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 09/29/2024

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