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- Title
The β-lactam-sensitived,d-carboxypeptidase activity of Pbp4 controls thel,d andd,d transpeptidation pathways in Corynebacterium jeikeium.
- Authors
Lavollay, Marie; Arthur, Michel; Fourgeaud, Martine; Dubost, Lionel; Marie, Arul; Riegel, Philippe; Gutmann, Laurent; Mainardi, Jean-Luc
- Abstract
Corynebacterium jeikeium is an emerging nosocomial pathogen responsible for vascular catheters infections, prosthetic endocarditis and septicemia. The treatment of C. jeikeium infections is complicated by the multiresistance of clinical isolates to antibiotics, in particular to β-lactams, the most broadly used class of antibiotics. To gain insight into the mechanism of β-lactam resistance, we have determined the structure of the peptidoglycan and shown that C. jeikeium has the dual capacity to catalyse formation of cross-links generated by transpeptidases of thed,d andl,d specificities. Two ampicillin-insensitive cross-linking enzymes were identified, LdtCjk1, a member of the active site cysteinel,d-transpeptidase family, and Pbp2c, a low-affinity class B penicillin-binding protein (PBP). In the absence of β-lactam, the PBPs and thel,d-transpeptidase contributed to the formation of 62% and 38% of the cross-links respectively. Although LdtCjk1 and Pbp2C were not inhibited by ampicillin, the participation of thel,d-transpeptidase to peptidoglycan cross-linking decreased in the presence of the drug. The specificity of LdtCjk1 for acyl donors containing a tetrapeptide stem accounts for this effect of ampicillin since the essential substrate of LdtCjk1 was produced by an ampicillin-sensitived,d-carboxypeptidase (Pbp4Cjk). Acquisition and mutational alterations of pbp2C accounted for high-level β-lactam resistance in C. jeikeium.
- Subjects
CORYNEBACTERIUM; NOSOCOMIAL infections; BETA lactam antibiotics; SEPSIS; ENDOCARDIUM diseases; ANTIBACTERIAL agents
- Publication
Molecular Microbiology, 2009, Vol 74, Issue 3, p650
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/j.1365-2958.2009.06887.x