ArticleAntimicrobial agents and chemotherapy2014
Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to β-lactam antibiotics.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 57 citations in OpenAlex.
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- Multifaceted Small Molecules as Enzyme Modulators: Cases of Drug Discovery/Repurposing Illustrating Nature's Pragmatism.BioMed research international · 2026Review
- Structure-Based Virtual Screening, ADMET Properties Prediction and Molecular Dynamics Studies Reveal Potential Inhibitors ofLife (Basel, Switzerland) · 2024Article
- Utilization of Existing Human Kinase Inhibitors as Scaffolds in the Development of New Antimicrobials.Antibiotics (Basel, Switzerland) · 2023Review
- ARGs Detection inMicroorganisms · 2023Article
- Synthetic and natural antimicrobials as a control against food borne pathogens: A review.Heliyon · 2023Review
- The Application of Cinnamon Twig Extract as an Inhibitor of Listeriolysin O againstMolecules (Basel, Switzerland) · 2023Article
- Article
- Identification of serine/threonine kinases that regulate metabolism and sporulation in Clostridium beijerinckii.Applied microbiology and biotechnology · 2022Article
- Identification of HPr kinase/phosphorylase inhibitors: novel antimicrobials against resistant Enterococcus faecalis.Journal of computer-aided molecular design · 2022Article
- Identification and Evaluation of Brominated Carbazoles as a Novel Antibiotic Adjuvant Scaffold in MRSA.ACS medicinal chemistry letters · 2022Article
- MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling.PLoS pathogens · 2022Article
- Inhibitors targeting the autophosphorylation of serine/threonine kinase ofFrontiers in microbiology · 2022Article
- Antimicrobial Resistance ofThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- IreK-Mediated, Cell Wall-Protective Phosphorylation inJournal of proteome research · 2021Article
- 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
- The enterococcal PASTA kinase: A sentinel for cell envelope stress.Molecular oral microbiology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.
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Registered trials
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