# Defining the impact of host factors on the molecular architecture and bacterial physiology of Staphylococcus aureus abscesses

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $800,040

## Abstract

PROJECT SUMMARY / ABSTRACT
 Staphylococcus aureus is capable of infecting nearly every vertebrate organ system, triggering the formation
of characteristic tissue lesions known as abscesses. Understanding how S. aureus survives within abscesses is
critical to the development of new therapeutics, as these lesions represent the pathogen niche during infection.
In this application, we will leverage a powerful mass spectrometry-based imaging platform to identify host and
bacterial factors that contribute to staphylococcal disease. By defining how tissue niche and host biology drive
molecular heterogeneity in abscesses, we will uncover new targets for tailored anti-staphylococcal therapeutics.
 Historically, it has been technically challenging to study the bacterial and host factors that contribute to
abscess physiology for two primary reasons. First, approaches that seek to preserve abscess architecture within
a tissue sample are inherently limited to the study of known microbial and host targets. This applies to techniques
such as immunohistochemistry and fluorescence in situ hybridization, which can define the spatial distribution of
analytes in a tissue but rely on pre-existing knowledge of targets. These approaches, by definition, cannot be
used to discover unknown bacterial or host factors that contribute to disease. Conversely, discovery-based
methods such as RNA sequencing or proteomics can identify novel, disease-associated analytes, but require
destructive tissue processing that eliminates information regarding the spatial orientation of microbial and host
molecules. To overcome these technical limitations, we created a mass spectrometry-based imaging platform to
identify host and microbial analytes in abscessed tissue during invasive S. aureus infection. Because imaging
mass spectrometry (IMS) does not require probes or detection reagents, this platform can define the localization
and abundance of abscess-associated analytes in a spatially-defined manner, thereby enabling the discovery of
microbial and host factors that contribute to disease pathogenesis. When applied to a model of disseminated S.
aureus infection, this IMS-based platform enabled three-dimensional molecular imaging of the staphylococcal-
host interface and powered the discovery of bacterial proteins that mark the pathogen niche within abscesses.
 Although individual abscesses typically have a similar histologic appearance, our IMS-based analysis
revealed significant molecular heterogeneity between S. aureus lesions. We hypothesize that abscesses display
molecular heterogeneity in response to tissue niche, antibacterial immune responses, and comorbid host
conditions. To test this hypothesis, we will couple our IMS platform with laser capture microdissection to enable
spatially-resolved proteomics of the staphylococcal-host interface. The proposed Aims will define the molecular
architecture of abscesses across S. aureus infected tissues and determine how innate immune effector...

## Key facts

- **NIH application ID:** 9973597
- **Project number:** 1R01AI145992-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** JAMES E CASSAT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $800,040
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973597

## Citation

> US National Institutes of Health, RePORTER application 9973597, Defining the impact of host factors on the molecular architecture and bacterial physiology of Staphylococcus aureus abscesses (1R01AI145992-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9973597. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*