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

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $229,500

## Abstract

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.

## Key facts

- **NIH application ID:** 10808578
- **Project number:** 1R21AI173725-01A1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Daniel E Voth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,500
- **Award type:** 1
- **Project period:** 2024-06-10 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808578

## Citation

> US National Institutes of Health, RePORTER application 10808578, Defining the impact of host-directed drugs on Coxiella burnetii growth in macrophages (1R21AI173725-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10808578. Licensed CC0.

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