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Antimicrobial Agents and Chemotherapy, May 2006, p. 1656-1663, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1656-1663.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Proteomic Study of Peptide Deformylase Inhibition in Streptococcus pneumoniae and Staphylococcus aureus

Vicuron Pharmaceuticals, 34790 Ardentech Court, Fremont, California 94555

Received 14 September 2005/ Returned for modification 30 January 2006/ Accepted 28 February 2006

Peptide deformylase (PDF) is an essential enzyme in both gram-negative and gram-positive bacteria. It hydrolyzes formylated N-terminal peptides to generate free N-terminal peptides during the process of protein maturation. Inhibition of this enzyme results in cessation of bacterial growth. We have examined the effect of a potent PDF inhibitor, LBM-415 (also known as VIC-104959), on the proteomes of Staphylococcus aureus and Streptococcus pneumoniae using two-dimensional electrophoresis. Both S. aureus and S. pneumoniae showed accumulation of many N-terminal formylated peptides/proteins upon PDF inhibition. In S. pneumoniae, formylated peptide/protein accumulation was time dependent. Following inhibition, subsequent removal of the inhibitor resulted in deformylation of formylated peptides/proteins; this recovery process was also time dependent. If instead the inhibited cells were maintained in the presence of sub-MIC levels of the PDF inhibitor, the formylated peptides/proteins remained for a much longer time, which correlated with a prolonged postantibiotic effect in vitro. These observations may have broader implications for the application of this class of antibiotics in vivo.