Abstract
The compound designated SB-219383 is a potent and selective inhibitor of bacterial tyrosyl tRNA synthetases. It exhibits an IC50 of < 1 nM against Staphylococcus aureus tyrosyl tRNA synthetase and weak in vitro activity against Staphylococci and Streptococci. Here we present data consistent with SB-219383 eliciting an amino acid starvation in both S. aureus and Streptococcus pneumoniae, supporting the conclusion that the antibacterial activity of SB-219383 is due to tyrosyl tRNA synthetase inhibition.
MeSH terms
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Culture Media
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Enzyme Inhibitors / pharmacology*
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Furans / pharmacology*
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Guanosine Tetraphosphate / metabolism
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Leucine / metabolism
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Micromonospora / metabolism*
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / growth & development
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Streptococcus pneumoniae / drug effects*
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Streptococcus pneumoniae / enzymology
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Streptococcus pneumoniae / growth & development
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Tyrosine-tRNA Ligase / antagonists & inhibitors*
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Uridine / metabolism
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Culture Media
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Enzyme Inhibitors
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Furans
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SB 219383
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Guanosine Tetraphosphate
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Tyrosine-tRNA Ligase
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Leucine
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Uridine