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
The 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)/lysin...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2011/306465 |
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| author | Narasimha Rao Uda Marc Creus |
| author_facet | Narasimha Rao Uda Marc Creus |
| author_sort | Narasimha Rao Uda |
| collection | DOAJ |
| description | The 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. |
| format | Article |
| id | doaj-art-38b15dfe3e0946dd84ddaa36f490165c |
| institution | Kabale University |
| issn | 1565-3633 1687-479X |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-38b15dfe3e0946dd84ddaa36f490165c2025-02-03T01:31:02ZengWileyBioinorganic Chemistry and Applications1565-36331687-479X2011-01-01201110.1155/2011/306465306465Selectivity 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 Uda0Marc Creus1Department of Chemistry, University of Basel, Spitalstrasse 51, Basel 4056, SwitzerlandDepartment of Chemistry, University of Basel, Spitalstrasse 51, Basel 4056, SwitzerlandThe 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.http://dx.doi.org/10.1155/2011/306465 |
| spellingShingle | Narasimha Rao Uda Marc Creus 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 Bioinorganic Chemistry and Applications |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2011/306465 |
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