Saturday, September 7, 2024
9/7/2024
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
