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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus
Jeyun Jo1, Tulsi Upadhyay1, Emily C Woods1
1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, United States.
Abstract:
Staphylococcus aureus (S. aureus) is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of S. aureus infections.
Insights
Researchers developed novel oxadiazolone probes to specifically image Staphylococcus aureus (S. aureus) infections. These probes target the S. aureus-specific enzyme FphE, enabling precise detection of bacterial biofilms.
Area of Science:
- Microbiology and Infectious Diseases
- Chemical Biology and Medicinal Chemistry
- Biotechnology and Medical Imaging
Background:
- Staphylococcus aureus (S. aureus) is a significant human pathogen causing diverse systemic infections.
- S. aureus biofilms present substantial challenges for clinical detection and treatment due to their in vivo persistence.
- Targeted imaging tools are crucial for effective clinical management of S. aureus infections.
Purpose of the Study:
- To develop novel oxadiazolone-based activity-based probes (ABPs) for specific imaging of S. aureus.
- To target the S. aureus-specific serine hydrolase FphE, an enzyme lacking homologues in other bacterial species.
- To validate FphE as a target for developing imaging contrast agents for rapid S. aureus detection.
Main Methods:
- Development of oxadiazolone-based activity-based probes.
- Utilizing X-ray crystallography to understand enzyme-probe interactions.
- Employing direct cell labeling and mouse models of infection for in vitro and in vivo validation.
Main Results:
- Oxadiazolone probes specifically labeled S. aureus bacteria.
- Labeling occurred via direct covalent modification of the FphE active site serine.
- Demonstrated the utility of oxadiazolone electrophiles for ABP development and FphE as a viable imaging target.
Conclusions:
- Oxadiazolone-based probes effectively and specifically target S. aureus via FphE.
- This approach enables precise imaging of S. aureus, including biofilms.
- Validated FphE as a promising target for developing novel diagnostic tools for S. aureus infections.
