Open AccessIdentification of a Dithiazoline Inhibitor of Escherichia coli l , d -Carboxypeptidase A
Author(s) -
Ellen Z. Baum,
Steven M. Crespo-Carbone,
Barbara D. Foleno,
Sean Peng,
Jamese J. Hilliard,
Darren Abbanat,
Raúl Goldschmidt,
Karen Bush
Publication year - 2005
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.49.11.4500-4507.2005
Subject(s) - escherichia coli , carboxypeptidase , tetrapeptide , biology , enzyme , peptidoglycan , biochemistry , lysis , microbiology and biotechnology , peptide , gene
The enzymel ,d -carboxypeptidase A is involved in the recycling of bacterial peptidoglycan and is essential inEscherichia coli during stationary phase. By high-throughput screening, we have identified a dithiazoline inhibitor of the enzyme with a 50% inhibitory concentration of 3 μM. The inhibitor appeared to cause lysis ofE. coli during stationary phase, behavior that is similar to a previously described deletion mutant ofl ,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 ofE. 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 asl ,d -carboxypeptidase A are largely underrepresented as targets of the antibiotic armamentarium but provide potential opportunities to interfere with bacterial growth and persistence.