# Coxiella manipulation of cholesterol in the intracellular niche

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $430,245

## Abstract

PROJECT SUMMARY/ABSTRACT
Coxiella burnetii is the causative agent of human Q fever, a zoonotic disease that can cause a debiliting, flu-
like illness in acute cases, or a life-threatening endocarditis in chronic patients. Q fever patients present with
few distinguishing clinical features, and chronic disease requires a minimum of 18 months of antibiotic
treatment, highlighting the need for new therapeutics. An obligate intracellular pathogen, Coxiella survives
inside a large, lysosome-like parasitophorous vacuole that is essential for bacterial replication and protects the
bacteria from the host immune response. The Coxiella parasitophorous vacuole (CPV) forms through
heterotypic fusion with host endosomes and autophagosomes, a process which also delivers cholesterol to the
CPV membrane. We recently determined that accumulation of host cholesterol in the CPV is toxic to the
bacteria, and hypothesize that Coxiella must deplete CPV cholesterol in order to survive within the host cell.
The objective of this application is to test our hypothesis that Coxiella uses two distinct mechanisms to
manipulate CPV cholesterol. Aim 1 will test the role of membrane contact sites in cholesterol transfer between
the CPV and the host endoplasmic reticulum. Aim 2 will determine the role of putative Coxiella sterol
reductases in modifying CPV cholesterol. At the conclusion of these studies, we will have elucidated how
Coxiella manipulates host cholesterol to maintain the optimal microenvironment for bacterial surivival.

## Key facts

- **NIH application ID:** 10135006
- **Project number:** 5R01AI139176-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** STACEY D GILK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,245
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135006

## Citation

> US National Institutes of Health, RePORTER application 10135006, Coxiella manipulation of cholesterol in the intracellular niche (5R01AI139176-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135006. Licensed CC0.

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