# Defining the role of post-translational regulation by extracellular proteases in the pathogenesis of Staphylococcus aureus osteomyelitis

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2021 · $451,808

## Abstract

SUMMARY ABSTRACT
We have demonstrated that mutation of the staphylococcal accessory regulatory (sarA) in Staphylococcus
aureus results in an increase in the production of extracellular proteases to a degree that limits biofilm
formation, limits cytotoxicity for mammalian cells including osteoblasts and osteoclasts, and limits the
accumulation of both surface-associated and extracellular virulence factors. We have also demonstrated that
this can be correlated with decreased virulence in animal models of sepsis and osteomyelitis. Moreover, we
have confirmed that all of these phenotypes are evident in diverse clinical isolates of S. aureus and that they
can be reversed by eliminating the ability of sarA mutants to produce extracellular proteases. In this proposal,
we will expand on these observations to identify the specific extracellular proteases that are most relevant in
the context of our underlying scientific hypothesis in diverse clinical isolates of S. aureus (Aim 1) and use the
information gained to interrogate the impact of these proteases on the virulence factor repertoire on these
clinical isolates, define the impact sarA and these proteases on bone remodeling and the host response in
bone infection, and ultimately identify and evaluate the contribution of specific S. aureus virulence factors alone
and in combination with each other on these phenotypes (Aim 2).

## Key facts

- **NIH application ID:** 10379698
- **Project number:** 2R01AI119380-06A1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** MARK S SMELTZER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $451,808
- **Award type:** 2
- **Project period:** 2015-06-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379698

## Citation

> US National Institutes of Health, RePORTER application 10379698, Defining the role of post-translational regulation by extracellular proteases in the pathogenesis of Staphylococcus aureus osteomyelitis (2R01AI119380-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10379698. Licensed CC0.

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