ArticleScientific reports2020
Inhibiting the two-component system GraXRS with verteporfin to combat Staphylococcus aureus infections.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- Punicalagin inhibits Staphylococcus aureus growth and biofilm formation: integrated omics reveals potential mechanisms.BMC microbiology · 2025Article
- DisarmingPathogens (Basel, Switzerland) · 2025Review
- Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2025Article
- First whole genome sequencing ofOpen veterinary journal · 2024Article
- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- Crosstalk involving two-component systems inJournal of bacteriology · 2024Review
- Anti-quorum sensing activity of poly-amidoamine dendrimer generation 5 dendrimer loaded kinase inhibitor peptide against methicillin-resistantSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Eye disease drug as a potential cure for COVID-19: one foot-in-the-door.Eye (London, England) · 2023Article
- Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials.Antibiotics (Basel, Switzerland) · 2021Review
- Bacterial Targets of Antibiotics in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Infections caused by Staphylococcus aureus pose a serious and sometimes fatal health issue. With the aim of exploring a novel therapeutic approach, we chose GraXRS, a Two-Component System (TCS) that determines bacterial resilience against host innate immune barriers, as an alternative target to disarm S. aureus. Following a drug repurposing methodology, and taking advantage of a singular staphylococcal strain that lacks the whole TCS machinery but the target one, we screened 1.280 off-patent FDA-approved drug for GraXRS inhibition. Reinforcing the connection between this signaling pathway and redox sensing, we found that antioxidant and redox-active molecules were capable of reducing the expression of the GraXRS regulon. Among all the compounds, verteporfin (VER) was really efficient in enhancing PMN-mediated bacterial killing, while topical administration of such drug in a murine model of surgical wound infection significantly reduced the bacterial load. Experiments relying on the chemical mimicry existing between VER and heme group suggest that redox active residue C227 of GraS participates in the inhibition exerted by this FDA-approved drug. Based on these results, we propose VER as a promising candidate for sensitizing S. aureus that could be helpful to combat persistent or antibiotic-resistant infections.
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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.