Related Experiment Video
Updated: Jun 16, 2026
07:10
A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Targeting the stringent response alters gene expression and extracellular vesicle RNA in Staphylococcus aureus
Sarah C Mansour1, Samuel J T Wardell2, Arjun S Baghela1
1Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Microbiology Spectrum
|June 15, 2026
Summary
Disrupting Staphylococcus aureus’s stringent response alters extracellular vesicle small RNAs and virulence. Targeting this pathway with compounds like DJK-5 weakens bacterial defenses, potentially enhancing antibiotic efficacy against resistant strains.
Area of Science:
- Microbiology
- Bacterial Physiology
- Molecular Biology
Background:
- The stringent response, mediated by (p)ppGpp, is crucial for *Staphylococcus aureus* survival under stress, impacting metabolism, antibiotic tolerance, and virulence.
- Extracellular vesicles (EVs) play a role in bacterial communication and virulence, with their cargo potentially influenced by cellular stress responses.
Purpose of the Study:
- To investigate the impact of disrupting the stringent response on the small RNA (sRNA) cargo of *S. aureus* EVs.
- To evaluate the effect of targeting the stringent response with a synthetic peptide (DJK-5) on bacterial gene expression, virulence, and antibiotic resistance.
Main Methods:
- Comparative analysis of EV-associated sRNAs from wild-type and stringent response mutant (*rsh*syn) *S. aureus* strains.
- Transcriptomic analysis of gene expression changes under stringent response-inducing conditions (mupirocin treatment).
- Assessment of the effects of synthetic peptide DJK-5 on bacterial gene expression, MRSA-mediated toxicity, and survival.
Main Results:
- Disruption of (p)ppGpp synthesis altered the sRNA cargo of *S. aureus* EVs, with SprX2 identified in mutant EVs.
- The stringent response mutant showed modest enhanced survival against vancomycin and oxacillin.
- Transcriptomic analysis revealed broad ppGpp-dependent gene expression remodeling, affecting amino acid biosynthesis, translation, adhesion, and virulence.
- DJK-5 treatment suppressed genes involved in adhesion, toxins, and exoenzymes, reduced MRSA toxicity, and lowered intracellular ppGpp levels.
Conclusions:
- Targeting the stringent response in *S. aureus* impacts both intracellular regulatory networks and EV-mediated signaling.
- Interfering with the stringent response pathway offers a potential strategy to attenuate *S. aureus* virulence and combat antibiotic resistance.
- The synthetic peptide DJK-5 demonstrates potential as a therapeutic agent to weaken bacterial defenses and enhance antibiotic effectiveness.
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