# Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $784,475

## Abstract

PROJECT SUMMARY
 Staphylococcus aureus is a major human pathogen that causes significant morbidity and mortality in both
hospital- and community-acquired infections. The appearance of multidrug-resistant strains has compounded
this problem, galvanizing efforts aimed at identifying new therapeutic targets. Staphylococcal infections are
characterized by the formation of tissue abscesses which represent the primary site of interaction between a
bacterial microcolony and the innate immune response of the host. We have discovered that the staphylococcal
abscess exhibits remarkable molecular heterogeneity, challenging efforts focused on designing therapeutics or
vaccines for the treatment and prevention of S. aureus infections. In this proposal, we will address this challenge
through the development of a cutting-edge multi-modal imaging platform that will define the molecular inventory
of the S. aureus abscess and reveal the contribution of host antimicrobials to the molecular composition of this
infectious interface.
 This proposal combines our expertise in immunology, infection biology, mass spectrometry, small animal
imaging, machine learning, and computer vision to develop an integrated multimodal visualization method for
studying microbial communities and tissue abscesses. Our unique approach will reveal the proteins, lipids, small
molecules, and transcripts that define the staphylococcal abscess. Through genetic inactivation of critical innate
immune effectors, we will uncover how the host response to infection drives alterations in these lesions. These
experiments will test the hypotheses that exposure to environmental stresses encountered within the host have
a powerful effect on molecular abundance and distribution within the staphylococcal microcolony, and that the
molecular environment of the abscess is highly variable and changes according to the stage of abscess
development.
 Taken together, our next-generation imaging capability will (i) map molecular heterogeneity within
microbial communities in response to environmental stressors, (ii) define molecular heterogeneity in tissue
abscesses, and (iii) determine molecular profiles and discover spatio-molecular host and microbial factors that
define the lifecycle of the staphylococcal abscess. These studies will uncover new targets for therapeutic
intervention against this important human pathogen, and the techniques developed as a result of this proposal
will be broadly applicable to all physiologically relevant processes, profoundly impacting biomedical research.

## Key facts

- **NIH application ID:** 10825355
- **Project number:** 2R01AI138581-06A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Eric P Skaar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $784,475
- **Award type:** 2
- **Project period:** 2018-09-19 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825355

## Citation

> US National Institutes of Health, RePORTER application 10825355, Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry (2R01AI138581-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10825355. Licensed CC0.

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