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Dynamics of the bacterial type IX secretion system and its effect on subgingival biofilm formation by bacteria of the human oral microbiome

Award Number: R00DE026826
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: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Dynamics of the bacterial type IX secretion system and its effect on subgingival biofilm formation by bacteria of the human oral microbiome - Project Summary/Abstract The bacterial Type IX protein secretion system (T9SS), which is a recently discovered protein secretion system, is found in bacteria that are a part of human subgingival biofilms. So far, it has been shown that T9SS is functional in Porphyromonas gingivalis [1, 2], Tannerella forsythia [3] and Capnocytophaga sp. [4]. P. gingivalis Arg-gingipain (Rgp) and Lys-gingipain (Kgp) are secreted via T9SS. Rgp and Kgp increase the risk of periodontal diseases by disrupting the host immune response and degradation of the host tissue and plasma proteins. T9SS is associated with a rotary motor and its dynamics enables secretion of cell-surface adhesins, known virulence factors and enzymes. It is also required for movement of bacteria over a surface by a process called gliding motility. Cell adhesion, surface navigation and motility are important for the formation of many bacterial biofilms [5]. Recent reports suggest that bacterial motility machineries enable sensing of external surfaces via a process called as mechanosensing [6, 7]. Human pathogens such as Escherichia coli and Salmonella enterica sense external surfaces via the flagellar motor-Type III secretion system machinery [6], while Pseudomonas aeruginosa and Myxococcus xanthus sense external surface via the Type IV pili machinery [7, 8]. Our preliminary and published results suggest that gliding bacteria with T9SS have the ability to sense external surfaces and viscous environments [9]. Such bacteria do not have the flagellar motor or the type IV pili. Amongst bacteria of the human oral microbiome, members of Capnocytophaga genus, which are present in human subgingival biofilms [10], are an attractive system for answering important questions related to biofilm formation, surface-sensing, and hydrodynamics. These bacteria have the T9SS and they exhibit gliding motility over external surfaces. Recently, genetic tools were developed for their manipulation [4]. I propose to study Capnocytophaga gingivalis, which is an important, yet understudied bacterium present in human subgingival biofilms [4, 10]. We discovered that the T9SS of C. gingivalis is powered by a novel rotary motor. Also, we found that C. gingivalis cells use adhesins secreted by T9SS to aggregate and form groups. Such aggregates exhibit gliding motility over external surfaces. Our data suggests that gliding is powered by the same rotary motor that powers secretion via T9SS. Gliding motility, which is the output of the dynamics of T9SS, will be used to assay for gene regulation and for development of genetic screens. Such screens will be targeted towards identification of proteins involved in sensory transduction by oral bacteria. Overall, dynamics of T9SS and role of proteins secreted by T9SS will be studied in the context of subgingival biofilm formation.


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 = -$522 )
2024	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	001	5	2/13/2024	NON-COMPETING CONTINUATION	-$522
2024	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	000	5	10/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = -$522

Issue Date FY: 2022 ( Subtotal = $240,506 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	000	5	3/16/2022	NON-COMPETING CONTINUATION	$240,506
														Subtotal = $240,506

Issue Date FY: 2021 ( Subtotal = $244,836 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	000	4	3/29/2021	NON-COMPETING CONTINUATION	$244,836
														Subtotal = $244,836

Issue Date FY: 2020 ( Subtotal = $249,000 )
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	000	3	4/8/2020	EXTENSION WITH OR WITHOUT FUNDS	$249,000
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Oral Diseases and Disorders Research	001	3	9/13/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $249,000

Grand Total All Awards = $733,820

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Dynamics of the bacterial type IX secretion system and its effect on subgingival biofilm formation by bacteria of the human oral microbiome

Award Number: R00DE026826

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: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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