Abstract
WalK, a histidine kinase, and WalR, a response regulator, make up a two-component signal transduction system that is indispensable for the cell-wall metabolism of low GC Gram-positive bacteria. WalK inhibitors are likely to show bactericidal effects against methicillin-resistant Staphylococcus aureus . We discovered a new WalK inhibitor, designated waldiomycin, by screening metabolites from actinomycetes. Waldiomycin belongs to the family of angucycline antibiotics and is structurally related to dioxamycin. Waldiomycin inhibits WalK from S. aureus and Bacillus subtilis at IC50s 8.8 and 10.2 μM, respectively, and shows antibacterial activity with MICs ranging from 4 to 8 μg ml(-1) against methicillin-resistant S. aureus and B. subtilis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / administration & dosage
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Bacillus subtilis / drug effects*
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Histidine Kinase
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Inhibitory Concentration 50
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Methicillin-Resistant Staphylococcus aureus / drug effects*
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Microbial Sensitivity Tests
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Protein Kinases / drug effects*
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Protein Kinases / metabolism
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Quinones / administration & dosage
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Quinones / chemistry
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Quinones / pharmacology*
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Signal Transduction / drug effects
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Streptomyces / metabolism
Substances
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Anti-Bacterial Agents
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Protein Kinase Inhibitors
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Quinones
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waldiomycin
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Protein Kinases
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Histidine Kinase