# A Novel Human Lung Infection Platform to Define Staphylococcus aureus Virulence Determinants

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $183,840

## Abstract

Project Summary
Staphylococcus aureus is a Gram-positive, opportunistic pathogen that causes severe nosocomial and
community-acquired pneumonia. In the lung, S. aureus encounters epithelial cells and macrophages, and recent
reports suggest these cells serve as a replication niche. However, conflicting information exists regarding the
ability of S. aureus to survive and replicate in host cells, specifically when comparing host species and bacterial
clonal lineages of differing degrees of virulence. Numerous studies have used animal models of infection and
human cell lines to study bacterial proliferation and the pro-inflammatory response to S. aureus; however, these
models do not entirely mimic the human condition due, in part, to critical virulence factors with species specificity.
The current proposal will establish a novel infection system that accurately mimics the interaction
between S. aureus and human lungs. Human lung tissue and isolated pulmonary cells will be exposed to
clinically relevant S. aureus isolates to investigate the pathogen's cellular replication niche and the host response
to infection. Aim 1 will characterize the target niche of S. aureus in the human lung and assess bacterial
replication in distinct cell types. Aim 2 will define the role of two S. aureus cytotoxins in triggering a pro-
inflammatory innate immune response and disrupting tissue integrity and cell survival. This Aim will use α-toxin
and Panton-Valentine Leukocidin as model virulence factors to establish our ex vivo infection system as a
disease-relevant method for defining virulence factor activity. Collectively, the proposed studies will
establish a human disease relevant infection platform to study pulmonary S. aureus infection and
virulence factor activity.

## Key facts

- **NIH application ID:** 9825517
- **Project number:** 5R21AI142056-02
- **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:** 2020
- **Award amount:** $183,840
- **Award type:** 5
- **Project period:** 2018-11-19 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825517

## Citation

> US National Institutes of Health, RePORTER application 9825517, A Novel Human Lung Infection Platform to Define Staphylococcus aureus Virulence Determinants (5R21AI142056-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9825517. Licensed CC0.

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