Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A
| Autor: | Steven M. Crespo-Carbone, Jamese J. Hilliard, Barbara D. Foleno, Raul Goldschmidt, Karen Bush, Sean Peng, Ellen Z. Baum, Darren Abbanat |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Carboxypeptidases A
Bacterial growth medicine.disease_cause Substrate Specificity chemistry.chemical_compound Enterobacteriaceae medicine Escherichia coli Pharmacology (medical) Protease Inhibitors Mechanisms of Action: Physiological Effects Pharmacology chemistry.chemical_classification biology biology.organism_classification Anti-Bacterial Agents Thiazoles Infectious Diseases Carboxypeptidase D Enzyme chemistry Biochemistry Carboxypeptidase A biology.protein Peptidoglycan Bacteria |
| Zdroj: | Antimicrobial agents and chemotherapy. 49(11) |
| ISSN: | 0066-4804 |
| Popis: | 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 μM. 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. |
| Databáze: | OpenAIRE |
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