# Molecular Mechanisms of Staphylococcus Epidermidis Strain Diversity

> **NIH NIH R01** · JACKSON LABORATORY · 2022 · $626,770

## Abstract

PROJECT SUMMARY / ABSTRACT
Staphylococcus epidermidis is a ubiquitous member of the human skin and mucosal microbiota. Functionally, it
is a key contributor to human health via immune modulation and microbial community homeostasis. Yet the
‘commensal’ S. epidermidis is also an important pathogen and disease risk reservoir—it is the most frequent
cause of medical device and bloodstream infections. Multiple phylogenetically diverse subspecies, or strains,
of S. epidermidis can co-inhabit the skin with genomes of variable gene content. The overwhelming majority of
these genes have unknown function. We hypothesize that this variable gene content, or accessory genome,
interacts with core genes to enable strains to uniquely respond to and thrive in different environments, and that
mixing of these genetically diverse strains is necessary to maintain a healthy homeostasis in the skin. To
investigate the function of these genes and to understand how genetic diversity at the strain level contributes to
population-level phenotype, we will functionally profile a set of phylogenetically diverse strains isolated from
healthy individuals and individuals with bloodstream infections. We will create CRISPRi tools for gene
knockdown in S. epidermidis to systematically identify strain-specific and core genes that underlie the ability to
colonize and compete in the skin and infections. Aim 1 develops the CRISPRi genetic toolkit to created pooled
S. epidermidis knockdown pools. Phenotypic profiling these pools will greatly expand our knowledge of
important commensal strategies employed by a common microbial partner, and how genetic heterogeneity
may impact the commensal to infectious transition. Aim 2 investigates the role of strain admixture in this
transition. This combination of genomic approaches and mechanistic studies will provide the first investigation
into the function of the S. epidermidis pangenome. Annotating inter-strain genetic diversity will reveal new
insights into the functional consequence of strain diversity: how strains can successfully transition between
commensal and virulence lifestyles, and how multiple strains can co-exist in an ecological network.

## Key facts

- **NIH application ID:** 10328966
- **Project number:** 5R01AR078634-02
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Julia Oh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $626,770
- **Award type:** 5
- **Project period:** 2021-01-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328966

## Citation

> US National Institutes of Health, RePORTER application 10328966, Molecular Mechanisms of Staphylococcus Epidermidis Strain Diversity (5R01AR078634-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328966. Licensed CC0.

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