# Metabolic determinants of Staphylococcus aureus skin colonization

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2023 · $69,500

## Abstract

PROJECT SUMMARY
 The human skin is the largest organ of the body. This physical barrier and the skin's innate immunity are
an essential first defense against pathogens. Staphylococcus aureus is an opportunistic pathogen and the
dominant microorganism of soft skin and tissue infections. These infections can quickly develop into systemic
infections and worsen health outcomes. Increasingly, antibiotic-resistant epidemic S. aureus strains (e.g.
methicillin-resistant S. aureus, MRSA) complicate treatment of these infections in the clinical setting.
 Although skin colonization increases risk of a MRSA infection, studying this aspect of host-pathogen
interactions has been challenging. Current animal models lack the acidity, skin structure, and eccrine gland
distribution of human skin and are not accessible to many research groups. Additionally, in vitro testing with
media mimicking the human skin surface have not been published. To address these gaps, I developed an in
vitro media that incorporates the metabolites, ions, and pH that MRSA would encounter on the human skin. I
performed RNA-seq of MRSA grown in these conditions and compared these results to a previous RNA-seq
experiment of MRSA inoculated on mouse skin. In both datasets, genes for metabolizing urea, derived from
sweat glands; and urocanic acid, derived from the natural moisturizing factor, were significantly upregulated. I
hypothesize that the metabolism of urea and urocanic acid contributes to S. aureus pH homeostasis and
growth, respectively, on the skin. This hypothesis will be tested in the following aims: Aim 1: Ascertain the
role of urease and related functions in MRSA growth and pH homeostasis in human skin-like in vitro models.
Genetic and biochemical approaches will be used in an in vitro media and a differentiated keratinocyte model to
investigate the role of urease, contribution of urea and nickel transport to urease function, and therapeutic
approaches to inhibit urease activity Aim 2: Investigate the role of urocanic acid metabolism in MRSA skin
colonization. Genetic and biochemical approaches will be used in the previously mentioned models to validate
the predicted encoded functions of this pathway, investigate substrate specificity of the pathway, and better
understand regulatory control. Epidemiology of pathway expression will be assessed by Western Blot analysis
of clinical S. aureus skin isolates from atopic dermatitis patients and healthy controls. These studies will
provide a foundation for future research of the skin microbiota, expand our understanding of MRSA
physiology on the skin, and identify potential targets for future therapeutic development.

## Key facts

- **NIH application ID:** 10749745
- **Project number:** 1F32AI172080-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Flavia Gisela Costa
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $69,500
- **Award type:** 1
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749745

## Citation

> US National Institutes of Health, RePORTER application 10749745, Metabolic determinants of Staphylococcus aureus skin colonization (1F32AI172080-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10749745. Licensed CC0.

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