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Investigating the role of Riboflavin and CidAB in Streptococcus mutans Anaerobic Metabolism

Award Number: F31DE029401
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: 05/15/2020
PERIOD OF PERFORMANCE END DATE: 08/15/2021

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Investigating the role of Riboflavin and CidAB in Streptococcus mutans Anaerobic Metabolism - Streptococcus mutans is a universal colonizer of the human oral cavity and is considered a primary causative agent of dental caries. The organism has evolved to utilize a wide variety sugars and macromolecules in order to generate energy which allows it to adapt to numerous environmental conditions. A common environmental condition encountered by S. mutans is near or complete anaerobiosis: life with little or no oxygen. This condition is often found in the oral cavity within complex, multi-species biofilms where nutrients are scarce and competition between species is fierce. One important molecule that must be successfully gleaned is riboflavin, an essential vitamin critical for co-factor generation as well as the activation of pyruvate formate lyase (PFL) by the PFL activating enzyme (PFL-AE). Recent work has indicated that the primary mechanism for S. mutans riboflavin acquisition lies proximal to a putative PFL-AE, which also is in close neighborhood association with genes encoding the CidAB proteins. Expression of cidAB is highly upregulated during anaerobic growth, under transcriptional control of CcpA, and this operon is important for S. mutans oxidative stress resistance. Furthermore, the LrgAB proteins (homologous to CidAB) have been shown to act as pyruvate transporters in Bacillus subtilis. Our collaborator's data indicates a similar role for LrgAB in S. mutans, and our lab's preliminary data suggests that CidAB functions in the transport and/or metabolism of formate in this organism. This data, combined with the predicted functions of genes within the chromosomal neighborhood of the cidAB operon, suggests an important role for this genomic region in anaerobic metabolism. This project seeks to better understand this aspect of S. mutans physiology by using a combination of genetic, metabolic, and proteomics approaches to interrogate a) how this organism obtains and metabolizes riboflavin during anaerobic growth using a novel molecular vitamin probe and b) how the CidAB proteins function in formate transport and/or metabolism by analyzing metabolite profiles and physiological changes during anaerobic growth. These objectives will advance our understanding as to how S. mutans is able to persist and compete within human oral cavity, and how the organism is able to adapt its complex metabolism to different environmental conditions. Furthermore, increased understanding of these processes will provide key insights into how S. mutans contributes to dental caries, as well as novel targets for anti-microbial therapeutics.


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 = -$1,924 )
2023	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	2	11/23/2022	NON-COMPETING CONTINUATION	-$1,924
														Subtotal = -$1,924

Issue Date FY: 2022 ( Subtotal = -$29,522 )
2022	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	2	11/16/2021	NON-COMPETING CONTINUATION	-$29,522
														Subtotal = -$29,522

Issue Date FY: 2021 ( Subtotal = $39,438 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	2	4/8/2021	NON-COMPETING CONTINUATION	$39,438
														Subtotal = $39,438

Issue Date FY: 2020 ( Subtotal = $38,140 )
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	1	12/26/2019	NEW	$0
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	003	1	2/26/2020	NEW	$0
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	002	1	2/12/2020	NEW	$504
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	1	12/26/2019	NEW	$37,636
														Subtotal = $38,140

Grand Total All Awards = $46,132

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Investigating the role of Riboflavin and CidAB in Streptococcus mutans Anaerobic Metabolism

Award Number: F31DE029401

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: 05/15/2020

PERIOD OF PERFORMANCE END DATE: 08/15/2021

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