title: Kinetic analysis of Enterococcus faecium L,D-transpeptidase inactivation by carbapenems.
abstract: Bypass of classical penicillin-binding proteins by the L,D-transpeptidase of Enterococcus faecium (Ldt(fm)) leads to high-level ampicillin resistance in E. faecium mutants, whereas carbapenems remain the lone highly active β-lactams. Kinetics of Ldt(fm) inactivation was determined for four commercial carbapenems and a derivative obtained by introducing a minimal ethyl group at position 2. We show that the bulky side chains of commercial carbapenems have both positive and negative effects in preventing hydrolysis of the acyl enzyme and impairing drug binding.
authors.affiliation: Centre de Recherche des Cordeliers, LRMA, Équipe 12, Université Pierre et Marie Curie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dubée
authors.forename: Michel
authors.initials: M
authors.lastname: Arthur
authors.forename: Hélène
authors.initials: H
authors.lastname: Fief
authors.forename: Sébastien
authors.initials: S
authors.lastname: Triboulet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Mainardi
authors.forename: Laurent
authors.initials: L
authors.lastname: Gutmann
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sollogoub
authors.forename: Louis B
authors.initials: LB
authors.lastname: Rice
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ethève-Quelquejeu
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Hugonnet
mesh_terms: D015780:Carbapenems / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D010458:Peptidyl Transferases / Q000378:metabolism*
chemical_list: D015780:Carbapenems; D010458:Peptidyl Transferases