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Confirmation of the antibacterial mode of action of SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp.

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.