ArticlePathogens (Basel, Switzerland)2015
Kinase Inhibitors that Increase the Sensitivity of Methicillin Resistant Staphylococcus aureus to β-Lactam Antibiotics.
Article in Pathogens (Basel, Switzerland), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Phosphorylation of a conserved intrinsically disordered region is necessary for activation of a bacterial Hanks-type Ser/Thr kinase signaling pathway.bioRxiv : the preprint server for biology · 2025Article
- Design, Synthesis, and Antimicrobial Evaluation of New Thiopyrimidine-Benzenesulfonamide Compounds.Molecules (Basel, Switzerland) · 2024Article
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Utilization of Existing Human Kinase Inhibitors as Scaffolds in the Development of New Antimicrobials.Antibiotics (Basel, Switzerland) · 2023Review
- Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance inScience signaling · 2023Article
- Comparative Study of the Difference in Behavior of the Accessory Gene Regulator (Agr) in USA300 and USA400 Community-Associated Methicillin-ResistantJournal of microbiology and biotechnology · 2021Article
- Review
- Interaction between β-lactam antibiotic and phosphorus-accumulating organisms.Environmental science and pollution research international · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-Molecules (Basel, Switzerland) · 2020Article
- Cinnamonitrile Adjuvants Restore Susceptibility to β-Lactams against Methicillin-ResistantACS medicinal chemistry letters · 2019Article
- Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.Current opinion in infectious diseases · 2019Review
- In Silico Screen and Structural Analysis Identifies Bacterial Kinase Inhibitors which Act with β-Lactams To Inhibit Mycobacterial Growth.Molecular pharmaceutics · 2018Article
- GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus.ACS infectious diseases · 2018Article
- Article
- Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound.Scientific reports · 2018Article
- Do Shoot the Messenger: PASTA Kinases as Virulence Determinants and Antibiotic Targets.Trends in microbiology · 2018Review
- Autophosphorylation Mechanism of the Ser/Thr Kinase Stk1 FromFrontiers in microbiology · 2018Article
- A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of theThe Journal of biological chemistry · 2017Article
- A novel STK1-targeted small-molecule as an "antibiotic resistance breaker" against multidrug-resistant Staphylococcus aureus.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Staphylococcus aureus are Gram-positive bacteria that are the leading cause of recurrent infections in humans that include pneumonia, bacteremia, osteomyelitis, arthritis, endocarditis, and toxic shock syndrome. The emergence of methicillin resistant S. aureus strains (MRSA) has imposed a significant concern in sustained measures of treatment against these infections. Recently, MRSA strains deficient in expression of a serine/threonine kinase (Stk1 or PknB) were described to exhibit increased sensitivity to β-lactam antibiotics. In this study, we screened a library consisting of 280 drug-like, low-molecular-weight compounds with the ability to inhibit protein kinases for those that increased the sensitivity of wild-type MRSA to β-lactams and then evaluated their toxicity in mice. We report the identification of four kinase inhibitors, the sulfonamides ST085384, ST085404, ST085405, and ST085399 that increased sensitivity of WT MRSA to sub-lethal concentrations of β-lactams. Furthermore, these inhibitors lacked alerting structures commonly associated with toxic effects, and toxicity was not observed with ST085384 or ST085405 in vivo in a murine model. These results suggest that kinase inhibitors may be useful in therapeutic strategies against MRSA 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.