# Staphylococcus serine hydrolases as targets for therapeutic and imaging contrast agents

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $348,216

## Abstract

Project Summary
Staphylococcus aureus is a major human pathogen that is the leading cause of infections worldwide. It is the
causative agent of multiple life threatening disease conditions including bacteremia, infectious endocarditis,
osteomyelitis, septic arthritis and prosthetic joint infection. A major complication to treatment is the fact that the
bacterium can form biofilms and infect locations that are hard to reach with systemic antibiotic administration.
In addition, diagnosis can often be difficult depending on the location of the infection, level of bacterial burden
and potential involvement of other bacterial species in the infection. Furthermore, S. aureus infections are often
more severe and management more complicated with greater number of interventions required compared to
other bacterial infections. Therefore novel strategies for rapid and effective diagnosis and treatment of S.
aureus infections have the potential to have significant clinical impact. This proposal outlines our plans to use
small molecule active site probes to identify serine hydrolases that are expressed by S. aureus bacteria. We
believe that secreted or surface exposed serine hydrolases are ideal targets for both novel small molecule anti-
virulence agents and for imaging contrast agents that can be used to non-invasively visualize sites of infection
in vivo. Our preliminary efforts have already identified 12 new uncharacterized serine hydrolases and we have
confirmed that at least one of these is involved in some aspect of virulence in the host. Therefore our primary
aims are to 1) Functionally characterize serine hydrolases in S. aureus to identify optimal targets for
imaging and therapeutic agents 2) Develop small molecule contrast agents and inhibitors that
selectively target serine hydrolases involved in pathogenesis 3) Validate hydrolase-specific imaging
probes and inhibitors in a mouse model of infection. Ultimately, success in these aims will not only lead to
identification and functional characterization of novel regulators of S. aureus pathogenesis but also to the
validation of imaging tools and inhibitors that could then be advanced to clinical applications in the future.
Ultimately, clinical validated imaging and therapy agents have the potential to impact detection, diagnosis and
therapy monitoring as well as to provide new ways to treat infection.

## Key facts

- **NIH application ID:** 10129383
- **Project number:** 5R01EB026332-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Matthew Bogyo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $348,216
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129383

## Citation

> US National Institutes of Health, RePORTER application 10129383, Staphylococcus serine hydrolases as targets for therapeutic and imaging contrast agents (5R01EB026332-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10129383. Licensed CC0.

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