Kinetic Analysis of Enterococcus faecium L,D-Transpeptidase Inactivation by Carbapenems

被引:22
作者
Dubee, Vincent [1 ,2 ,3 ]
Arthur, Michel [1 ,2 ,3 ]
Fief, Helene [4 ,5 ]
Triboulet, Sebastien [1 ,2 ,3 ]
Mainardi, Jean-Luc [1 ,2 ,3 ,6 ]
Gutmann, Laurent [1 ,2 ,3 ,6 ]
Sollogoub, Matthieu [4 ,5 ]
Rice, Louis B. [7 ]
Etheve-Quelquejeu, Melanie [4 ,5 ]
Hugonnet, Jean-Emmanuel [1 ,2 ,3 ]
机构
[1] Univ Paris 06, Ctr Rech Cordeliers, LRMA, Equipe 12, Paris, France
[2] INSERM, U872, Paris, France
[3] Univ Paris 05, Paris, France
[4] Univ Paris 06, Inst Parisien Chim Mol, Equipe GOBS, Paris, France
[5] CNRS, Paris, France
[6] Hop Europeen Georges Pompidou, AP HP, Paris, France
[7] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA
关键词
PEPTIDOGLYCAN CROSS-LINKING; MYCOBACTERIUM-TUBERCULOSIS; TRANSPEPTIDASE; BIOSYNTHESIS; ANTIBIOTICS; CLAVULANATE; RESISTANCE; MEROPENEM;
D O I
10.1128/AAC.06398-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 beta-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.
引用
收藏
页码:3409 / 3412
页数:4
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