# Coxiella survival mechanisms in the intracellular niche

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $543,926

## Abstract

PROJECT SUMMARY/ABSTRACT
Coxiella burnetii is the causative agent of human Q fever, a zoonotic disease that can cause a debilitating, flu-
like illness in acute cases, or a life-threatening endocarditis in chronically infected 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 vacuole within infected cells that has characteristics of a functional phagolysosome, including
active proteases and phosphatases and moderately acidic pH, a physicochemical parameter to which C. burnetii
is exquisitely adapted. C. burnetii is a strict moderate acidophile capable of efficient nutrient transport, catabolism
and replication only within a narrow pH range under both host cell-free and intracellular conditions. The objective
of this application is to identify host and pathogen factors that function to maintain both CCV and bacterial
cytoplasmic pH. Aim 1 will test the hypothesis that C. burnetii controls bacterial cytoplasmic pH via carbonic
anhydrase-dependent metabolism of CO2 and also how the metabolically dormant Small Cell Variant of C.
burnetii protects the pathogen against acid stress. Aim 2 will test the hypothesis that C. burnetii regulates CCV
pH by manipulating host lysosomal biogenesis. Understanding the molecular mechanisms behind C. burnetii
survival within the acidic CCV will allow identification of potential therapeutic targets.

## Key facts

- **NIH application ID:** 10862736
- **Project number:** 5R01AI155560-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** STACEY D GILK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,926
- **Award type:** 5
- **Project period:** 2022-07-13 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862736

## Citation

> US National Institutes of Health, RePORTER application 10862736, Coxiella survival mechanisms in the intracellular niche (5R01AI155560-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10862736. Licensed CC0.

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