Evolution of peptidoglycan biosynthesis under the selective pressure of antibiotics in Gram-positive bacteria

被引:133
|
作者
Mainardi, Jean-Luc [1 ,2 ,3 ,4 ]
Villet, Regis [1 ,2 ,3 ]
Bugg, Timothy D. [5 ]
Mayer, Claudine [1 ,2 ,3 ]
Arthur, Michel [1 ,2 ,3 ]
机构
[1] Ctr Rech Cordeliers, LRMA, INSERM, U872, F-75270 Paris 06, France
[2] Univ Paris 06, UMR 872, Paris, France
[3] Univ Paris 05, UMR 872, Paris, France
[4] Hop Europeen Georges Pompidou, AP HP, Paris, France
[5] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
关键词
antibiotic resistance; beta-lactam; glycopeptide; Gram-positive bacteria; peptidoglycan synthesis;
D O I
10.1111/j.1574-6976.2007.00097.x
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Acquisition of resistance to the two classes of antibiotics therapeutically used against Gram-positive bacteria, the glycopeptides and the beta-lactams, has revealed an unexpected flexibility in the peptidoglycan assembly pathway. Glycopeptides select for diversification of the fifth position of stem pentapeptides because replacement of D-Ala by D-lactate or D-Ser at this position prevents binding of the drugs to peptidoglycan precursors. The substitution is generally well tolerated by the classical D,D-transpeptidases belonging to the penicillin-binding protein family, except by low-affinity enzymes. Total elimination of the fifth residue by a D,D-carboxypeptidase requires a novel cross-linking enzyme able to process the resulting tetrapeptide stems. This enzyme, an L,D-transpeptidase, confers cross-resistance to beta-lactams and glycopeptides. Diversification of the side chain of the precursors, presumably in response to the selective pressure of peptidoglycan endopeptidases, is controlled by aminoacyl transferases of the Fem family that redirect specific aminoacyl-tRNAs from translation to peptidoglycan synthesis. Diversification of the side chains has been accompanied by a parallel divergent evolution of the substrate specificity of the L,D-transpeptidases, in contrast to the D,D-transpeptidases, which display an unexpected broad specificity. This review focuses on the role of antibiotics in selecting or counter-selecting diversification of the structure of peptidoglycan precursors and their mode of polymerization.
引用
收藏
页码:386 / 408
页数:23
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