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Significance of Corneal Cell Invasion by Bacteria

Award Number: R01EY011221
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1995
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Significance of Corneal Cell Invasion by Bacteria - Summary: P. aeruginosa is a leading cause of blinding eye disease. Contributing to disease pathogenesis is invasion of corneal epithelial cells, as we have demonstrated in vitro and in vivo. Here, we report that P. aeruginosa can establish multiple niches inside corneal epithelial cells, some colonizing the cytoplasm and other vacuoles – often in the same cell. Reporter expression results show different phenotypic states in these alternate locations, the pattern suggesting “acute” infection mode for cytoplasmic bacteria and “chronic” (biofilm forming) mode for those in vacuoles. While genetic regulation of the switch between these two states has been extensively studied in vitro, how this might work inside a cell is unknown. Our published and preliminary data show that “acute” and “chronic” modes cooperate to determine corneal epithelial cell responses, to allow P. aeruginosa to penetrate the multilayered corneal epithelium, to colonize the cornea, and to cause pathology. Here, we will test the hypothesis that their unique intracellular niches contribute to their cooperative efforts during corneal infection. The three aims will explore significance of intracellular diversification to the bacteria, to the host corneal epithelial cell, and to disease pathogenesis. Approaches will utilize multiple novel tools developed using funding from this grant, including bacterial constructs, imaging technologies, and infection models. The two consultants are leading experts in bacterial gene regulation, respectively covering both phenotypes. Importantly, our data suggest that vacuolar P. aeruginosa transition into biofilms, which can be difficult to kill or even to culture. A vacuole would enclose a biofilm inside two host membranes - vacuolar and plasma. This intracellular phenotype alone could explain why P. aeruginosa infections are notoriously difficult to manage and why disease can continue despite apparent sterilization of the ulcer.


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 = $401,250 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	26	7/1/2024	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $401,250

Issue Date FY: 2023 ( Subtotal = $401,250 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	25	7/3/2023	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $401,250

Issue Date FY: 2022 ( Subtotal = $389,213 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	24	6/10/2022	NON-COMPETING CONTINUATION	$389,213
														Subtotal = $389,213

Issue Date FY: 2021 ( Subtotal = $389,212 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	002	23	6/10/2021	NON-COMPETING CONTINUATION	$389,212
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	001	22	5/25/2021	COMPETING CONTINUATION	$38,191
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	21	5/25/2021	NON-COMPETING CONTINUATION	-$38,191
														Subtotal = $389,212

Issue Date FY: 2020 ( Subtotal = $397,500 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	001	22	7/7/2020	COMPETING CONTINUATION	$397,500
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	21	6/30/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $397,500

Issue Date FY: 2019 ( Subtotal = $392,500 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	21	11/15/2018	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2018 ( Subtotal = $392,500 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	20	5/3/2018	NON-COMPETING CONTINUATION	$39,250
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	20	11/17/2017	NON-COMPETING CONTINUATION	$353,250
														Subtotal = $392,500

Issue Date FY: 2017 ( Subtotal = $392,500 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	19	7/10/2017	NON-COMPETING CONTINUATION	$39,250
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	19	11/17/2016	NON-COMPETING CONTINUATION	$353,250
														Subtotal = $392,500

Issue Date FY: 2016 ( Subtotal = $392,500 )
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	18	2/10/2016	NON-COMPETING CONTINUATION	$39,250
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	18	12/3/2015	NON-COMPETING CONTINUATION	$353,250
														Subtotal = $392,500

Issue Date FY: 2015 ( Subtotal = $391,771 )
2015	2015	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	17	12/18/2014	COMPETING CONTINUATION	$391,771
2015	2013	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	16	12/15/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $391,771

Issue Date FY: 2013 ( Subtotal = $349,980 )
2013	2013	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	16	9/5/2013	NON-COMPETING CONTINUATION	$349,980
														Subtotal = $349,980

Issue Date FY: 2012 ( Subtotal = $368,400 )
2012	2012	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	15	8/6/2012	NON-COMPETING CONTINUATION	$368,400
														Subtotal = $368,400

Issue Date FY: 2011 ( Subtotal = $368,400 )
2011	2011	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	14	8/23/2011	NON-COMPETING CONTINUATION	$368,400
														Subtotal = $368,400

Issue Date FY: 2010 ( Subtotal = $383,750 )
2010	2010	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	13	8/9/2010	COMPETING CONTINUATION	$383,750
2010	2009	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	12	8/5/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,750

Issue Date FY: 2009 ( Subtotal = $302,334 )
2009	2009	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	12	4/7/2009	NON-COMPETING CONTINUATION	$302,334
														Subtotal = $302,334

Issue Date FY: 2008 ( Subtotal = $343,676 )
2008	2008	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	001	11	4/25/2008	SUPPLEMENT FOR EXPANSION	$54,385
2008	2008	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	11	4/21/2008	NON-COMPETING CONTINUATION	$289,291
														Subtotal = $343,676

Issue Date FY: 2007 ( Subtotal = $295,195 )
2007	2007	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	10	3/16/2007	NON-COMPETING CONTINUATION	$295,195
														Subtotal = $295,195

Issue Date FY: 2006 ( Subtotal = $296,856 )
2006	2006	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	9	3/8/2006	NON-COMPETING CONTINUATION	$296,856
														Subtotal = $296,856

Issue Date FY: 2005 ( Subtotal = $304,000 )
2005	2005	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	000	8	5/26/2005	COMPETING CONTINUATION	$304,000
														Subtotal = $304,000

Issue Date FY: 2004 ( Subtotal = $142,243 )
2004	2004	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Vision Research	002	7	9/24/2004	SUPPLEMENT FOR EXPANSION	$142,243
														Subtotal = $142,243

Issue Date FY: 2003 ( Subtotal = $142,243 ) (Continued on the next page)
Grand Total All Awards = $8,118,746

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Significance of Corneal Cell Invasion by Bacteria

Award Number: R01EY011221

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/1995

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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