Wednesday, September 17, 2025 9/17/2025

Candidalysin: a key mediator of Candida vaginitis immunopathology

Award Number: R01AI134796
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: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2024

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Candidalysin: a key mediator of Candida vaginitis immunopathology - Candida albicans, the primary causative agent of fungal vaginitis, will affect 75% of all women of reproductive age at least once in their lifetime. Long believed to result from immunodeficiency, a growing body of evidence strongly suggests that vaginitis is now considered to be an immunopathology, in which the host response actually drives disease symptoms. Lack of a comprehensive understanding of the host and fungal factors that initiate symptomatic disease high remains a barrier to progress in better treating and managing this most prevalent human fungal infection. Guided by strong preliminary data, we have identified the newly described fungal toxin Candidalysin as the major virulence factor governing vaginitis pathogenesis. Therefore, the objective of this proposal is to determine if variation in expression or activity of Candidalysin in clinical isolates governs C. albicans pathogenicity at the vaginal mucosa. These aims will test our central hypothesis that variation in Candidalysin activity partly underlies the variable symptomatology of Candida vaginal colonization and identification of host signaling engaged by Candidalysin may elucidate new molecular therapeutic targets. Under the first aim, we will determine amino acid residues that contribute to reduced pathogenicity of a variant Candidalysin observed in clinical isolates. We will also determine differential host responses to wild-type and variant Candidalysin at the vaginal mucosa. The second aim will focus on identifying prevalent genetic mechanisms (promoter sequences, Kex proteases) that control Candidalysin expression and function. We will confirm these by functional level by allelic transfers between strong and weak Candidalysin expressing strains. The third aim seeks to identify host factors elicited by Candidalysin that may drive immunopathology in vivo and determine if blockade of these signaling mechanisms can alleviate symptomatic disease. The outcomes of this project will provide foundational information regarding function of Candidalysin isoforms, genetic checkpoints of Candidalysin expression, and identify promising new pathways that may be exploited for the clinical management of vaginitis.


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: 2025 ( Subtotal = $441,284 )
2025	2025	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	6	12/17/2024	NON-COMPETING CONTINUATION	$441,284
2025	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	002	5	1/21/2025	COMPETING CONTINUATION	$46,314
2025	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	001	4	1/21/2025	NON-COMPETING CONTINUATION	-$46,314
														Subtotal = $441,284

Issue Date FY: 2024 ( Subtotal = $461,861 )
2024	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	002	5	9/4/2024	COMPETING CONTINUATION	$46,186
2024	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	001	5	2/1/2024	COMPETING CONTINUATION	$415,675
2024	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	4	1/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $461,861

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	4	7/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $380,000 )
2021	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	4	8/9/2021	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2020 ( Subtotal = $380,000 )
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	3	8/5/2020	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2019 ( Subtotal = $380,000 )
2019	2019	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	2	7/31/2019	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2018 ( Subtotal = $380,000 )
2018	2018	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Allergy and Infectious Diseases Research	000	1	8/21/2018	NEW	$380,000
														Subtotal = $380,000

Grand Total All Awards = $2,423,145

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Candidalysin: a key mediator of Candida vaginitis immunopathology

Award Number: R01AI134796

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: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2024

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