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Selectivity of Inhibition of N-Succinyl-L, L-diaminopimelic acid desuccinylase in bacteria : the product of dapE-gene is not the target of L-Captopril antimicrobial activity

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Hindawi Publ.
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  • Biology
  • Chemistry

Abstract

Journal Menu Abstracting and Indexing Aims and Scope Annual Issues Article Processing Charges Articles in Press Author Guidelines Bibliographic Information Contact Information Editorial Board Editorial Workflow Free eTOC Alerts Reviewers Acknowledgment Subscription Information Open Special Issues Published Special Issues Special Issue Guidelines Abstract Full-Text PDF Full-Text HTML Linked References How to Cite this Article Bioinorganic Chemistry and ApplicationsVolume 2011 (2011), Article ID 306465, 6 pagesdoi:10.1155/2011/306465Research ArticleSelectivity of Inhibition of N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase in Bacteria: The product of dapE-gene Is Not the Target of L-Captopril Antimicrobial ActivityNarasimha Rao Uda and Marc CreusDepartment of Chemistry, University of Basel, Spitalstrasse 51, Basel 4056, SwitzerlandReceived 22 December 2010; Accepted 21 January 2011Academic Editor: Zheng Dong Copyright © 2011 Narasimha Rao Uda and Marc Creus. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractThe emergence of bacterial strains that are resistant to virtually all currently available antibiotics underscores the importance of developing new antimicrobial compounds. N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a metallohydrolase involved in the meso-diaminopimelate (mDAP)/lysine biosynthetic pathway necessary for lysine biosynthesis and for building the peptidoglycan cell wall. Because DapE is essential for Gram-negative and some Gram-positive bacteria, DapE has been proposed as a good target for antibiotic development. Recently, L-captopril has been suggested as a lead compound for inhibition of DapE, although its selectivity for this enzyme target in bacteria remains unclear (Gillner et al. (2009)). Here, we tested the selectivity of L-captopril against DapE in bacteria. Since DapE knockout strains of gram-negative bacteria are viable upon chemical supplementation with mDAP, we reasoned that the antimicrobial activity of compounds targeting DapE should be abolished in mDAP-containing media. Although L-captopril had modest antimicrobial activity in Escherichia coli and in Salmonella enterica, to our surprise, inhibition of bacterial growth was independent both of mDAP supplementation and DapE over-expression. We conclude that DapE is not the main target of L-captopril inhibition in these bacteria. The methods implemented here will be useful for screening DapE-selective antimicrobial compounds directly in bacterial cultures.

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