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Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmission

Award Number: R01AI102584
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2012
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmission - PROJECT SUMMARY Vibrio cholerae causes the disease cholera, an important public health problem worldwide. V. cholerae’s ability to cause epidemics is tied to its dissemination and survival in aquatic habitats and its transmission to the human host. The pathogen’s ability to form biofilms (i.e., matrix-enclosed, surface-associated communities) is crucial for its survival in aquatic habitats between epidemics and is advantageous for host-to-host transmission during epidemics. The signaling nucleotide cyclic dimeric guanosine monophosphate (c-diGMP) is broadly conserved in bacteria and is a key regulator of biofilm formation. Understanding of how c-diGMP controls biofilm formation, which environmental signals modulate c-diGMP levels and biofilm formation, and consequences of c-diGMP signaling in V. cholerae infectivity, transmission and dissemination, is limited. These information gaps will addressed by focusing on two specific aims. 1) Analyze c-diGMP signaling pathways that control biofilm formation dynamics; and 2) Analyze activation of c-diGMP signaling pathways and their consequences in V. cholerae infection cycle. Under the first aim, the molecular mechanism(s) through which c-diGMP controls production of the type IVa MSHA pilus, the primary component of initial surface attachment will be determined using structural and biochemical approaches. The down-stream c-diGMP signaling pathways initiated upon surface attachment will be analyzed by employing microscopy-based community tracking methods to measure motility, division, and second messenger signal levels. The mechanism by which specific key c-diGMP signaling proteins act to control surface attachment and biofilm matrix production will be determined using combination of genetic and biochemical approaches. Under the second aim, the mechanism of activation of key c-diGMP signaling proteins will be determined using structural and ligand binding studies. The role of c-diGMP signaling in in vivo biofilm formation, in V. cholerae transmission and dissemination will also be investigated, using state- of-the-art imaging tools and novel c-diGMP sensors. The proposed work will greatly advance the understanding of how c-diGMP signaling operates, identify the inputs that influence c-diGMP production and degradation, and unveil the biological consequences of c-diGMP signaling. The proposed work promises molecular/mechanistic insights that will allow us to devise ways to control c-di-GMP signal transduction pathways governing motility and biofilm formation, ultimately providing targets for the development of inhibitors of V. cholerae transmission.


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: 2026 ( Subtotal = $0 )
2026	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	10	1/20/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $671,384 )
2023	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	10	6/1/2023	NON-COMPETING CONTINUATION	$671,384
														Subtotal = $671,384

Issue Date FY: 2022 ( Subtotal = $673,208 )
2022	2022	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	9	5/19/2022	NON-COMPETING CONTINUATION	$673,208
														Subtotal = $673,208

Issue Date FY: 2021 ( Subtotal = $772,840 )
2021	2021	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	8	4/29/2021	NON-COMPETING CONTINUATION	$693,091
2021	2021	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	001	8	8/18/2021	NON-COMPETING CONTINUATION	$79,749
														Subtotal = $772,840

Issue Date FY: 2020 ( Subtotal = $709,261 )
2020	2020	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	002	7	5/20/2020	NON-COMPETING CONTINUATION	$709,261
2020	2019	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	001	6	2/4/2020	COMPETING CONTINUATION	$204,560
2020	2017	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	5	2/4/2020	NON-COMPETING CONTINUATION	-$204,560
														Subtotal = $709,261

Issue Date FY: 2019 ( Subtotal = $757,971 )
2019	2019	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	6	5/28/2019	COMPETING CONTINUATION	$757,971
														Subtotal = $757,971

Issue Date FY: 2017 ( Subtotal = $825,515 )
2017	2017	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	003	5	5/18/2017	NON-COMPETING CONTINUATION	$631,747
2017	2016	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	002	4	2/1/2017	EXTENSION WITH OR WITHOUT FUNDS	$112,845
2017	2015	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	001	3	2/1/2017	NON-COMPETING CONTINUATION	-$112,845
2017	2014	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	2	1/25/2017	NON-COMPETING CONTINUATION	$193,768
														Subtotal = $825,515

Issue Date FY: 2016 ( Subtotal = $634,687 )
2016	2016	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	4	5/26/2016	EXTENSION WITH OR WITHOUT FUNDS	$634,687
														Subtotal = $634,687

Issue Date FY: 2015 ( Subtotal = $629,175 )
2015	2015	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	3	5/14/2015	NON-COMPETING CONTINUATION	$629,175
														Subtotal = $629,175

Issue Date FY: 2014 ( Subtotal = $627,522 )
2014	2014	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	2	5/6/2014	NON-COMPETING CONTINUATION	$627,522
														Subtotal = $627,522

Issue Date FY: 2013 ( Subtotal = $428,277 )
2013	2013	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	1	5/22/2013	NEW	$428,277
														Subtotal = $428,277

Grand Total All Awards = $6,729,840

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Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmission

Award Number: R01AI102584

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/10/2012

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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