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Staphylococcus aureus Survival During Nutrient Restriction and Suppression of Host Immunity.

Award Number: R01AI120994
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: 01/15/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Staphylococcus aureus Survival During Nutrient Restriction and Suppression of Host Immunity. - Project Summary Staphylococcus aureus (Sa) is a leading cause of nosocomial infection in the United States and is a predominant pathogen in communities. Treatment of Sa infections is complicated by the prevalence of antibiotic resistant and highly virulent clones, making new therapeutic alternatives a necessity. Sa survives during infection by subverting immune defenses and adapting to host-imposed nutrient restriction. Yet, we lack a unifying understanding of these adaptations to the host environment, which complicates the development of new therapeutics and vaccines. We recently discovered that a cofactor required for metabolic enzyme complex function and potent antioxidant, lipoic acid (LA), is a critical mediator of Sa growth and survival during infection. Furthermore, we found that Sa releases the lipoylated E2 subunit of the metabolic enzyme complex pyruvate dehydrogenase to blunt protective innate immune responses via its LA moiety. Thus, our work has uncovered a mechanism of Sa survival during infection that links bacterial metabolism and nutrient acquisition to defense against innate immunity. Despite establishing these roles for LA biosynthesis and salvage in Sa pathobiology, there exist major gaps in our understanding of the mechanics of how LA blunts immunity and promotes optimal metabolism during infection. Notably: (i) the precise mechanism by which bacterial LA-protein blunts immune activation has not been elucidated; (ii) regulation of LA distribution on essential metabolic enzymes is not understood; (iii) the role of LA in mediating defense against oxidative stress has not been investigated; and (iv) the relevance of LA acquisition to survival in different infection sites is not understood. This renewal application will address these gaps in knowledge by ascertaining precisely how LA subverts immunity and the mechanics of LA synthesis/salvage that promote bacterial survival in vivo with the potential to lay the groundwork for new targeted therapeutics. Aim 1 will determine how bacterial-derived LA blunts immune responses. Aim 2 will determine how Sa regulates LA salvage and distribution. Aim 3 will investigate how accessibility to host nutrients in different tissues determines the requirement for LA during infection.


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 = $440,000 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	11	3/11/2025	NON-COMPETING CONTINUATION	$440,000
														Subtotal = $440,000

Issue Date FY: 2024 ( Subtotal = $459,189 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	10	2/1/2024	NON-COMPETING CONTINUATION	$413,271
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	001	10	5/23/2024	NON-COMPETING CONTINUATION	$45,918
2024	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	003	8	7/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$27,962
2024	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	002	7	7/25/2024	NON-COMPETING CONTINUATION	-$27,962
														Subtotal = $459,189

Issue Date FY: 2023 ( Subtotal = $489,170 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	002	9	3/17/2023	NON-COMPETING CONTINUATION	$463,338
2023	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	001	8	11/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$423,561
2023	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	7	11/21/2022	NON-COMPETING CONTINUATION	-$397,729
														Subtotal = $489,170

Issue Date FY: 2022 ( Subtotal = $442,331 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	7	2/18/2022	NON-COMPETING CONTINUATION	$442,331
														Subtotal = $442,331

Issue Date FY: 2021 ( Subtotal = $445,899 )
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	002	6	9/28/2021	COMPETING CONTINUATION	$112,473
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	6	3/8/2021	COMPETING CONTINUATION	$445,899
2021	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	001	5	9/28/2021	NON-COMPETING CONTINUATION	-$112,473
														Subtotal = $445,899

Issue Date FY: 2020 ( Subtotal = $364,666 )
2020	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	5	1/30/2020	NON-COMPETING CONTINUATION	$364,666
														Subtotal = $364,666

Issue Date FY: 2019 ( Subtotal = $364,666 )
2019	2019	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	4	1/11/2019	NON-COMPETING CONTINUATION	$364,666
														Subtotal = $364,666

Issue Date FY: 2018 ( Subtotal = $364,666 )
2018	2018	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	3	1/12/2018	NON-COMPETING CONTINUATION	$364,666
														Subtotal = $364,666

Issue Date FY: 2017 ( Subtotal = $364,666 )
2017	2017	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	2	1/11/2017	NON-COMPETING CONTINUATION	$364,666
														Subtotal = $364,666

Issue Date FY: 2016 ( Subtotal = $364,666 )
2016	2016	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	1	1/15/2016	NEW	$364,666
														Subtotal = $364,666

Grand Total All Awards = $4,099,919

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Staphylococcus aureus Survival During Nutrient Restriction and Suppression of Host Immunity.

Award Number: R01AI120994

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: 01/15/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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