Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A.

Abstract

The enzyme L,D-carboxypeptidase A is involved in the recycling of bacterial peptidoglycan and is essential in Escherichia coli during stationary phase. By high-throughput screening, we have identified a dithiazoline inhibitor of the enzyme with a 50% inhibitory concentration of 3 microM. The inhibitor appeared to cause lysis of E. coli during stationary phase, behavior that is similar to a previously described deletion mutant of L,D-carboxypeptidase A (M. F. Templin, A. Ursinus, and J.-V. Holtje, EMBO J. 18:4108-4117, 1999). As much as a one-log drop in CFU in stationary phase was observed upon treatment of E. coli with the inhibitor, and the amount of intracellular tetrapeptide substrate increased by approximately 33%, consistent with inhibition of the enzyme within bacterial cells. Stationary-phase targets such as L,D-carboxypeptidase A are largely underrepresented as targets of the antibiotic armamentarium but provide potential opportunities to interfere with bacterial growth and persistence.

Cite this paper

@article{Baum2005IdentificationOA, title={Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A.}, author={Ellen Z Baum and Steven M. Crespo-Carbone and Barbara D Foleno and Sean X. Peng and Jamese J. Hilliard and Darren Abbanat and Raul M Goldschmidt and Karen Bush}, journal={Antimicrobial agents and chemotherapy}, year={2005}, volume={49 11}, pages={4500-7} }