HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 18, 13151-13159, May 4, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/18/13151    most recent M610911200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Magnet, S. Articles by Arthur, M. Search for Related Content PubMed PubMed Citation Articles by Magnet, S. Articles by Arthur, M. Social Bookmarking                      What's this?

Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes^*

Sophie Magnet^¶, Ana Arbeloa^¶, Jean-Luc Mainardi^¶||, Jean-Emmanuel Hugonnet^¶, Martine Fourgeaud^¶, Lionel Dubost^**, Arul Marie^**, Vanessa Delfosse^¶, Claudine Mayer^¶, Louis B. Rice, and Michel Arthur^¶1

From the INSERM, U655-LRMA F-75006 Paris France, Université Pierre et Marie Curie-Paris6, Centre de Recherches Biomédicales des Cordeliers, F-75006 Paris, France, ^¶Université Paris-Descartes, Facultéde Médecine René Descartes, Centre de Recherches Biomédicales des Cordeliers, F-75006 Paris, France, ^||AP-HP, Hôpital Européen Georges Pompidou, F-75015 Paris, France, ^**Plateforme de Spectrométrie de Masse et de Protéomique, Muséum National d'Histoire Naturelle, Département Recherche Développement et Diversité Moléculaire, F-75005 Paris, France, and Medical and Research Services, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106

We report here the first direct assessment of the specificity of a class of peptidoglycan cross-linking enzymes, the L,D-transpeptidases, for the highly diverse structure of peptidoglycan precursors of Gram-positive bacteria. The lone functionally characterized member of this new family of active site cysteine peptidases, Ldt_fm from Enterococcus faecium, was previously shown to bypass the D,D-transpeptidase activity of the classical penicillin-binding proteins leading to high level cross-resistance to glycopeptide and -lactam antibiotics. Ldt_fm homologues from Bacillus subtilis (Ldt_Bs) and E. faecalis (Ldt_fs) were found here to cross-link their cognate disaccharide-peptide subunits containing meso-diaminopimelic acid (mesoDAP³) and L-Lys³-L-Ala-L-Ala at the third position of the stem peptide, respectively, instead of L-Lys³-D-iAsn in E. faecium. Ldt_fs differed from Ldt_fm and Ldt_Bs by its capacity to hydrolyze the L-Lys³-D-Ala⁴ bond of tetrapeptide (L,D-carboxypeptidase activity) and pentapeptide (L,D-endopeptidase activity) stems, in addition to the common cross-linking activity. The three enzymes were specific for their cognate acyl acceptors in the cross-linking reaction. In contrast to Ldt_fs, which was also specific for its cognate acyl donor, Ldt_fm tolerated substitution of L-Lys³-D-iAsn by L-Lys³-L-Ala-L-Ala. Likewise, Ldt_Bs tolerated substitution of mesoDAP³ by L-Lys³-D-iAsn and L-Lys³-L-Ala-L-Ala in the acyl donor. Thus, diversification of the structure of peptidoglycan precursors associated with speciation has led to a parallel evolution of the substrate specificity of the L,D-transpeptidases affecting mainly the recognition of the acyl acceptor. Blocking the assembly of the side chain could therefore be used to combat antibiotic resistance involving L,D-transpeptidases.

Received for publication, November 27, 2006 , and in revised form, January 18, 2007.

^* This work was supported by the program "ACI Microbiologie 2003" from the Fonds National de la Science (Grant ACIM-4-9), the European Community (COBRA, contract LSHM-CT-2003-503335, 6th PCRD), NIAID, National Institutes of Health (Grant R01 AI45626), and the Fondation pour la Recherche Médicale. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: INSERM U655-LRMA, Université Pierre et Marie Curie Centre de Recherches Biomédicales des Cordeliers, 15 Rue de l'Ecole de Médecine, 75270 Paris, Cedex 06, France. Tel.: 33-1-43-25-00-33; Fax: 33-1-43-25-68-12; E-mail: michel.arthur{at}bhdc.jussieu.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Magnet, L. Dubost, A. Marie, M. Arthur, and L. Gutmann Identification of the L,D-Transpeptidases for Peptidoglycan Cross-Linking in Escherichia coli J. Bacteriol., July 1, 2008; 190(13): 4782 - 4785. [Abstract] [Full Text] [PDF]

				M. Lavollay, M. Arthur, M. Fourgeaud, L. Dubost, A. Marie, N. Veziris, D. Blanot, L. Gutmann, and J.-L. Mainardi The Peptidoglycan of Stationary-Phase Mycobacterium tuberculosis Predominantly Contains Cross-Links Generated by L,D-Transpeptidation J. Bacteriol., June 15, 2008; 190(12): 4360 - 4366. [Abstract] [Full Text] [PDF]

				E. C. Hett and E. J. Rubin Bacterial Growth and Cell Division: a Mycobacterial Perspective Microbiol. Mol. Biol. Rev., March 1, 2008; 72(1): 126 - 156. [Abstract] [Full Text] [PDF]

				J.-L. Mainardi, J.-E. Hugonnet, F. Rusconi, M. Fourgeaud, L. Dubost, A. N. Moumi, V. Delfosse, C. Mayer, L. Gutmann, L. B. Rice, et al. Unexpected Inhibition of Peptidoglycan LD-Transpeptidase from Enterococcus faecium by the beta-Lactam Imipenem J. Biol. Chem., October 19, 2007; 282(42): 30414 - 30422. [Abstract] [Full Text] [PDF]

				S. Magnet, S. Bellais, L. Dubost, M. Fourgeaud, J.-L. Mainardi, S. Petit-Frere, A. Marie, D. Mengin-Lecreulx, M. Arthur, and L. Gutmann Identification of the L,D-Transpeptidases Responsible for Attachment of the Braun Lipoprotein to Escherichia coli Peptidoglycan J. Bacteriol., May 15, 2007; 189(10): 3927 - 3931. [Abstract] [Full Text] [PDF]