ArticleScientific reports2017
A novel STK1-targeted small-molecule as an "antibiotic resistance breaker" against multidrug-resistant Staphylococcus aureus.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Integrated Genome-Wide Association Study and Machine Learning Approach for Characterizing the Determinants of Biofilm Formation in Staphylococcus aureus.Interdisciplinary sciences, computational life sciences · 2026Article
- Dual host and pathogen targeting by MEK1/2 inhibitors.Infection and immunity · 2026Review
- Emerging therapeutic drug targets in amino acid and protein biosynthesis pathways against ESKAPE and non-ESKAPE pathogens: a comprehensive review.Archives of microbiology · 2026Review
- Structural and evolutionary insights into understudied bacterial serine-threonine pseudokinase families.Biochemical Society transactions · 2025Review
- Targeting the MEK1/2 pathway to combatmBio · 2025Article
- Loratadine decreases virulence of methicillin-resistantbioRxiv : the preprint server for biology · 2025Article
- An atlas of bacterial serine-threonine kinases reveals functional diversity and key distinctions from eukaryotic kinases.Science signaling · 2025Article
- Loratadine Combats Methicillin-ResistantACS infectious diseases · 2024Article
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Comparative Genomics Identifies Novel Genetic Changes Associated with Oxacillin, Vancomycin and Daptomycin Susceptibility in ST100 Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance inScience signaling · 2023Article
- Brominated Carbazole with Antibiotic Adjuvant Activity Displays Pleiotropic Effects in MRSA's Transcriptome.ACS chemical biology · 2022Article
- Identification and Evaluation of Brominated Carbazoles as a Novel Antibiotic Adjuvant Scaffold in MRSA.ACS medicinal chemistry letters · 2022Article
- The In Vitro Antimicrobial and Antibiofilm Activities of Lysozyme against Gram-Positive Bacteria.Computational and mathematical methods in medicine · 2022Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- PASTA kinase-dependent control of peptidoglycan synthesis via ReoM is required for cell wall stress responses, cytosolic survival, and virulence in Listeria monocytogenes.PLoS pathogens · 2021Article
- Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Article
- Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.Current opinion in infectious diseases · 2019Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Ser/Thr protein kinase (STK1) plays a critical role in cell wall biosynthesis of and drug resistance in methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains lacking STK1 become susceptible to failing cephalosporins, such as Ceftriaxone and Cefotaxime. STK1, despite being nonessential protein for MRSA survival, it can serve as an important therapeutic agent for combination therapy. Here, we report a novel small molecule quinazoline compound, Inh2-B1, which specifically inhibits STK1 activity by directly binding to its ATP-binding catalytic domain. Functional analyses encompassing in vitro growth inhibition of MRSA, and in vivo protection studies in mice against the lethal MRSA challenge indicated that at high concentration neither Inh2-B1 nor Ceftriaxone or Cefotaxime alone was able to inhibit the growth of bacteria or protect the challenged mice. However, the growth of MRSA was inhibited, and a significant protection in mice against the bacterial challenge was observed at a micromolar concentration of Ceftriaxone or Cefotaxime in the presence of Inh2-B1. Cell-dependent minimal to no toxicity of Inh2-B1, and its abilities to down-regulate cell wall hydrolase genes and disrupt the biofilm formation of MRSA clearly indicated that Inh2-B1 serves as a therapeutically important "antibiotic-resistance-breaker," which enhances the bactericidal activity of Ceftriaxone/Cefotaxime against highly pathogenic MRSA infection.
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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.