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Defining the impact of host-directed drugs on Coxiella burnetii growth in macrophages

Award Number: R21AI173725
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: 06/10/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Defining the impact of host-directed drugs on Coxiella burnetii growth in macrophages - Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever. Q fever presents most often as an acute flu-like illness but can present as fatal chronic endocarditis. Unfortunately, treatment options for Q fever endocarditis are highly ineffective and require many months of antibiotic administration. We recently discovered numerous host-directed drugs that suppress C. burnetii replication within the pathogen’s target cell, the human macrophage. These drugs, which are typically used to treat psychosis- or mood-related disorders by inhibiting neurotransmitter (NTM) system signaling, potentially represent novel anti-Q fever therapies. The current proposal will define the impact of NTM-acting drugs on the ability of C. burnetii to replicate within alveolar macrophages and regulate the macrophage innate immune response to infection. Aim 1 will define the specific NTM machinery involved in C. burnetii replication in macrophages. Aim 2 will define the impact of host-directed drugs on the pathogen’s ability to dampen the cytokine response and shift alveolar macrophages to a pro-replication, anti-inflammatory phenotype. Throughout the proposal, we will use primary human alveolar macrophages and human precision-cut lung slices to provide disease relevance. Collectively, the current proposal will lay the groundwork to characterize novel anti-C. burnetii treatments.


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 = $0 )
2026	2025	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	2	3/4/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $191,250 )
2025	2025	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	2	4/18/2025	NON-COMPETING CONTINUATION	$191,250
														Subtotal = $191,250

Issue Date FY: 2024 ( Subtotal = $229,500 )
2024	2024	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$22,950
2024	2024	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	1	6/10/2024	NEW	$206,550
														Subtotal = $229,500

Grand Total All Awards = $420,750

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Defining the impact of host-directed drugs on Coxiella burnetii growth in macrophages

Award Number: R21AI173725

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: 06/10/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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