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Plasma membrane promotes stress resistance and virulence of Candida albicans

Award Number: R01AI047837
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The human fungal pathogen Candida albicans is a leading cause of hospital-acquired bloodstream infections and can disseminate to become lethal. There is an urgent need to improve the therapeutic management of C. albicans infections, since current antifungal drugs have limited effectiveness and drug-resistant strains are emerging. The pathogenic effects of C. albicans are caused by its ability to grow in the host and disseminate to internal organs. The plasma membrane is fundamentally important for these processes, as this essential barrier mediates a wide range of functions that are critical for virulence including cell wall synthesis, secretion of virulence factors, morphogenesis, and nutrient uptake. The importance of the plasma membrane is highlighted by the fact that it is the target for most of the currently used antifungal drugs and many antimicrobial peptides. Therefore, a better understanding of plasma membrane organization and function is needed to facilitate the design of new therapeutic treatments and to increase the effectiveness of current antifungal drugs. To address this gap in knowledge, the Aims are designed to take advantage of recent discoveries to identify novel mechanisms by which the plasma membrane protects C. albicans from stressful conditions in the host. Aim 1 is to define the mechanisms that protect the plasma membrane against the oxidative burst in the host, which can cause a chain reaction of lipid peroxidation that destroys membrane integrity. These studies will leverage our recent identification of a new pathway that protects C. albicans against lipid peroxidation. Aim 2 will define how the PM resists stress caused by HOCl (hypochlorous acid; bleach) that is produced by myeloperoxidase during the neutrophil oxidative burst. Although neutrophils are well known to produce HOCl, little is known about its effects on the plasma membrane or how C. albicans protects against it. Aim 3 is to define how the C. albicans PM plays a key role in resisting copper and cell wall stress, which are also encountered in the phagosome. This aim takes advantage of our discovery that specialized plasma membrane subdomains known as eisosomes or MCC domains promote proper PM architecture needed for resistance to copper and cell wall stress. Defining how the C. albicans plasma membrane resists stress is expected to reveal novel mechanisms of pathogenesis that will aid future studies in development of new therapeutic approaches and increase our understanding of current antifungal drugs to improve the prospects for their more effective use.


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 = $528,804 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	22	4/18/2024	NON-COMPETING CONTINUATION	$528,804
														Subtotal = $528,804

Issue Date FY: 2023 ( Subtotal = $528,804 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	21	4/11/2023	NON-COMPETING CONTINUATION	$528,804
2023	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	20	2/9/2023	COMPETING CONTINUATION	$102,151
2023	2021	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	19	2/9/2023	NON-COMPETING CONTINUATION	-$102,151
														Subtotal = $528,804

Issue Date FY: 2022 ( Subtotal = $528,804 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	20	5/5/2022	COMPETING CONTINUATION	$528,804
2022	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	19	4/27/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $528,804

Issue Date FY: 2021 ( Subtotal = $443,446 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	19	12/15/2020	NON-COMPETING CONTINUATION	$443,446
														Subtotal = $443,446

Issue Date FY: 2020 ( Subtotal = $443,446 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	18	12/16/2019	NON-COMPETING CONTINUATION	$443,446
														Subtotal = $443,446

Issue Date FY: 2019 ( Subtotal = $443,446 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	17	12/21/2018	NON-COMPETING CONTINUATION	$443,446
														Subtotal = $443,446

Issue Date FY: 2018 ( Subtotal = $442,757 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	16	12/15/2017	NON-COMPETING CONTINUATION	$442,757
														Subtotal = $442,757

Issue Date FY: 2017 ( Subtotal = $545,450 )
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	004	15	5/5/2017	COMPETING CONTINUATION	$0
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	15	1/17/2017	COMPETING CONTINUATION	$440,692
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	15	3/23/2017	COMPETING CONTINUATION	-$220,590
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	15	4/4/2017	COMPETING CONTINUATION	$421,956
2017	2015	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	14	2/24/2017	NON-COMPETING CONTINUATION	-$96,608
														Subtotal = $545,450

Issue Date FY: 2015 ( Subtotal = $390,142 )
2015	2015	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	14	6/19/2015	NON-COMPETING CONTINUATION	$390,142
														Subtotal = $390,142

Issue Date FY: 2014 ( Subtotal = $390,142 )
2014	2014	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	13	7/2/2014	NON-COMPETING CONTINUATION	$390,142
														Subtotal = $390,142

Issue Date FY: 2013 ( Subtotal = $370,223 )
2013	2013	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	12	7/19/2013	NON-COMPETING CONTINUATION	$370,223
														Subtotal = $370,223

Issue Date FY: 2012 ( Subtotal = $387,827 )
2012	2012	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	11	8/17/2012	COMPETING CONTINUATION	$387,827
														Subtotal = $387,827

Issue Date FY: 2010 ( Subtotal = $289,151 )
2010	2010	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	6/7/2010	NON-COMPETING CONTINUATION	$289,151
														Subtotal = $289,151

Issue Date FY: 2009 ( Subtotal = $292,072 )
2009	2009	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	9	7/7/2009	NON-COMPETING CONTINUATION	$292,072
														Subtotal = $292,072

Issue Date FY: 2008 ( Subtotal = $292,072 )
2008	2008	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	8	6/17/2008	NON-COMPETING CONTINUATION	$292,072
														Subtotal = $292,072

Issue Date FY: 2007 ( Subtotal = $297,729 )
2007	2007	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	7	4/27/2007	NON-COMPETING CONTINUATION	$297,729
														Subtotal = $297,729

Issue Date FY: 2006 ( Subtotal = $306,621 )
2006	2006	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	6	6/19/2006	COMPETING CONTINUATION	$306,621
														Subtotal = $306,621

Issue Date FY: 2005 ( Subtotal = $225,750 )
2005	2005	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Microbiology and Infectious Diseases Research	000	5	1/21/2005	NON-COMPETING CONTINUATION	$225,750
														Subtotal = $225,750

Issue Date FY: 2004 ( Subtotal = $225,750 )
2004	2004	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Microbiology and Infectious Diseases Research	000	4	1/29/2004	NON-COMPETING CONTINUATION	$225,750
														Subtotal = $225,750

Issue Date FY: 2003 ( Subtotal = $225,750 )
2003	2003	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Microbiology and Infectious Diseases Research	000	3		NON-COMPETING CONTINUATION	$225,750
														Subtotal = $225,750

Issue Date FY: 2002 ( Subtotal = $225,750 )
2002	2002	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Microbiology and Infectious Diseases Research	000	2	1/11/2002	NON-COMPETING CONTINUATION	$225,750
														Subtotal = $225,750

Issue Date FY: 2001 ( Subtotal = $222,468 ) (Continued on the next page)
Grand Total All Awards = $8,046,404

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Plasma membrane promotes stress resistance and virulence of Candida albicans

Award Number: R01AI047837

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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