ArticleThe Journal of biological chemistry2024
Discovery of an antivirulence compound that targets the Staphylococcus aureus SaeRS two-component system to inhibit toxic shock syndrome toxin-1 production.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed.
- Elucidating the Staphylococcus aureus TSST-1 Regulatory Network as a Response to Vaginal pH.Molecular microbiology · 2026Article
- Transcriptomic profiling of TSST-1-induced cytotoxicity and inflammatory responses in human vaginal epithelial cells.BMC microbiology · 2026Article
- Article
- Perspectives on engineering and biomaterials in tampon design: a review of device-tissue interactions and dysmenorrhea risk.Frontiers in bioengineering and biotechnology · 2026Review
- Pyrimidine sufficiency is required for Sae two-component system signaling inJournal of bacteriology · 2025Article
- Linking Virulence and Iron Limitation Response inJournal of proteome research · 2025Article
- Toxic Shock Syndrome Toxin-1 (TSST-1) inToxins · 2025Review
- AACS synthetic biology · 2025Article
- DisarmingPathogens (Basel, Switzerland) · 2025Review
- CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis inJournal of bacteriology · 2024Article
- Functional Study ofInfection and drug resistance · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Menstrual toxic shock syndrome (mTSS) is a rare but severe disorder associated with the use of menstrual products such as high-absorbency tampons and is caused by Staphylococcus aureus strains that produce the toxic shock syndrome toxin-1 (TSST-1) superantigen. Herein, we screened a library of 3920 small bioactive molecules for the ability to inhibit transcription of the TSST-1 gene without inhibiting the growth of S. aureus. The dominant positive regulator of TSST-1 is the SaeRS two-component system (TCS), and we identified phenazopyridine hydrochloride (PP-HCl) that repressed the production of TSST-1 by inhibiting the kinase function of SaeS. PP-HCl competed with ATP for binding of the kinase SaeS leading to decreased phosphorylation of SaeR and reduced expression of TSST-1 as well as several other secreted virulence factors known to be regulated by SaeRS. PP-HCl targets the virulence of S. aureus, and it also decreases the impact of TSST-1 on human lymphocytes without affecting the healthy vaginal microbiota. Our findings demonstrate the promising potential of PP-HCl as a therapeutic strategy against mTSS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.