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Pathogenic and protective roles of strain-specific P. acnes hyaluronidases in acne

Award Number: R01AI141401
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: 07/18/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Pathogenic and protective roles of strain-specific P. acnes hyaluronidases in acne - Abstract Acne is an important skin disorder believed to be caused by skin commensal P. acnes, although how P. acnes contributes to acne is unclear. We have identified two types of hyaluronidase enzymes, made by different strains of P. acnes, that are either pro- or anti-inflammatory. Importantly, skin colonization by P. acnes strains that encode the pro-inflammatory hyaluronidase is associated with development of acne, whereas colonization with P. acnes strains that express the anti-inflammatory hyaluronidase is associated with healthy skin. In preliminary experiments, we have shown that the pro- or anti-inflammatory property of the hyaluronidases is related to the size of hyaluronan fragments generated by the enzymes. Therefore, we hypothesize that hyaluronidases influence the acne-genic potential of P. acnes by degrading hyaluronan to different sizes. To address our hypothesis, 1) we propose to investigate the structural basis of hyaluronan degradation by P. acnes hyaluronidases, binding of hyaluronan fragments to TLR2/4 and host immune responses to the hyaluronan fragments. 2) We propose to determine the contribution of both hyaluronidases to acne by testing well characterized clinical strains of P. acnes and mutant strains of P. acnes that do not express hyaluronidase, in a new mouse acne model. 3) We will also investigate hyaluronidase-based strategies for preventing or treating acne.


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: 2023 ( Subtotal = $479,531 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	6/16/2023	NON-COMPETING CONTINUATION	$479,531
														Subtotal = $479,531

Issue Date FY: 2022 ( Subtotal = $491,254 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	4	6/24/2022	NON-COMPETING CONTINUATION	$491,254
														Subtotal = $491,254

Issue Date FY: 2021 ( Subtotal = $601,122 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	3	6/29/2021	NON-COMPETING CONTINUATION	$601,122
														Subtotal = $601,122

Issue Date FY: 2020 ( Subtotal = $675,242 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	6/25/2020	NON-COMPETING CONTINUATION	$675,242
														Subtotal = $675,242

Issue Date FY: 2019 ( Subtotal = $480,729 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	7/17/2019	NEW	$480,729
														Subtotal = $480,729

Grand Total All Awards = $2,727,878

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Pathogenic and protective roles of strain-specific P. acnes hyaluronidases in acne

Award Number: R01AI141401

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: 07/18/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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