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Manipulation of the host cell inflammasome by Mycobacterium tuberculosis

Award Number: R01AI147630
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: 06/08/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Manipulation of the host cell inflammasome by Mycobacterium tuberculosis - Abstract Mycobacterium tuberculosis (Mtb) causes pulmonary tuberculosis (TB) in humans. In 2017 alone, ~10.0 million new cases were reported, leading to approximately ~1.3 million deaths. There are no effective vaccines for TB and only sub-optimal chemotherapeutics exist. IL-1 is a cytokine that increases host resistance against Mtb infections. Mtb is able to limit the amount of IL-1 production by inhibiting the host cell inflammasome activation. There is a gap in our understanding of how Mtb exploits host cell signaling in order to inhibit the activation of the inflammasome. We describe for the first time that Mtb can inhibit the activation of the NLRP3 inflammasome and we identified the first Mtb gene (PknF) important for this inhibition. We performed a gain-of-function genetic screen and identified 5 other genomic regions of Mtb mediating the inhibition of the AIM2 inflammasome. We think that the discovery of specific Mtb genes involved in inhibiting the host inflammasome activation (Specific Aim 1) will allow for the characterization of the molecular mechanisms of inhibition (Specific Aim 2) and for testing their importance for virulence of Mtb (Specific Aim 3) during the course of the research proposal. We believe that our findings will have great translational potential since a greater understanding of the molecular mechanisms of host cell inflammasome activation will provide novel targets for development of adjunctive Mtb drugs and of host-directed therapeutics.


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: 2026 ( Subtotal = $592,882 )
2026	2026	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	5/28/2026	NON-COMPETING CONTINUATION	$592,882
														Subtotal = $592,882

Issue Date FY: 2025 ( Subtotal = $592,882 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	8/21/2025	NON-COMPETING CONTINUATION	$592,882
														Subtotal = $592,882

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	6/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $585,157 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	5/4/2023	NON-COMPETING CONTINUATION	$585,157
														Subtotal = $585,157

Issue Date FY: 2022 ( Subtotal = $599,019 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	2	5/9/2022	NON-COMPETING CONTINUATION	$599,019
														Subtotal = $599,019

Issue Date FY: 2021 ( Subtotal = $629,786 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	6/8/2021	NEW	$629,786
														Subtotal = $629,786

Grand Total All Awards = $2,999,726

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Manipulation of the host cell inflammasome by Mycobacterium tuberculosis

Award Number: R01AI147630

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: 06/08/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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