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Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria

Award Number: K99DE029228
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria - Project Summary/Abstract Dental caries is the most common chronic infectious disease globally and is caused by the formation of acid- producing bacterial biofilms on the tooth surface, which demineralize and destroy the protective underlying enamel barrier. Although the efficacy of fluoride treatments (the contemporary standard in caries prevention) is well-documented, the current prevalence of the disease clearly illustrates that fluoride alone is insufficient to prevent caries in many situations. Therefore, increased understanding of disease pathogenesis and exploration of novel preventative strategies are objectives worthy of attention. Regardless of the microbial taxa involved, bacterial acid-tolerance is an indispensable factor in caries pathogenesis. The known caries pathogen Streptococcus mutans increases the proportion of unsaturated fatty acids (UFAs) in its plasma membrane in response to environmental acidification—an adaptation required for acid-tolerance and virulence. Preliminary data indicates that several other Gram-positive oral taxa, including the caries-associated species, Lactobacillus casei, modify their membranes in a similar manner in response to environmental acidification. This proposal addresses a number of currently unanswered questions raised by these observations. Aims 1 and 2 of the proposed research will determine the scope of this response to acid stress across the oral microbiome, in single taxa or in a community setting. Aim 3 of this proposal will elucidate how these UFAs are protective against acid- mediated damage. These aims will be accomplished using bioinformatics tools, basic molecular microbiology, an ecologically-relevant and complex in vitro oral biofilm model, and mass spectrometry/lipidomics. Successful completion of the proposed research will answer pertinent questions regarding caries pathogenesis in a multi- species setting and is likely to open the door to investigation of novel anti-caries therapeutics which, while targeting acidophiles, function regardless of the presence and abundance of S. mutans. The candidate, Dr. Jonathon Baker, has a longstanding interest in the microbiology of dental caries. Upon completion of the K99 (mentored) phase of this award, his goal is to become an independent PI at a leading research university, where he plans to continue research on the modifications that bacteria make to their membranes to combat environmental stresses, while leveraging acquired data to develop novel therapeutics. A funded K99/R00 proposal will allow Dr. Baker to develop skills necessary to both complete the proposed research (training in mass spectrometry/lipidomics) and subsequently become an independent research scientist (training in didactic lecturing, mentoring, and grantsmanship). Dr. Baker’s mentors, Drs. Victor Nizet and Pieter Dorrestein, and environment (J. Craig Venter Institute and UC San Diego) have been carefully selected to provide high-quality, diverse scientific and collegial support, as well as state-of-the-art facilities, to ensure successful completion of this research program and the proposed career development goals.


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 = -$22,249 )
2024	2022	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	000	2	2/21/2024	SUPPLEMENT FOR EXPANSION	-$22,249
														Subtotal = -$22,249

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	001	2	9/11/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2021	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	000	2	9/11/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $130,902 )
2022	2022	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	001	2	6/21/2022	SUPPLEMENT FOR EXPANSION	$130,902
2022	2021	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	000	2	6/21/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $130,902

Issue Date FY: 2021 ( Subtotal = $130,902 )
2021	2021	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	000	2	6/8/2021	NON-COMPETING CONTINUATION	$130,902
														Subtotal = $130,902

Issue Date FY: 2020 ( Subtotal = $130,902 )
2020	2020	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Oral Diseases and Disorders Research	000	1	5/29/2020	NEW	$130,902
														Subtotal = $130,902

Grand Total All Awards = $370,457

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Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria

Award Number: K99DE029228

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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