Mainardi, Jean-Luc, Villet, Regis, Bugg, Tim, Mayer, Claudine and Arthur, Michel (2008) Evolution of peptidoglycan biosynthesis under the selective pressure of antibiotics in Gram-positive bacteria. FEMS Microbiology Reviews, Vol.32 (No.2). pp. 386-408. ISSN 0168-6445

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Abstract

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.

Item Type:	Journal Item
Subjects:	Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Drug resistance in microorganisms, Beta lactam antibiotics, Glycopeptide antibiotics, Gram-positive bacteria, Peptidoglycans -- Synthesis
Journal or Publication Title:	FEMS Microbiology Reviews
Publisher:	Blackwell Publishing
ISSN:	0168-6445
Date:	March 2008
Volume:	Vol.32
Number:	No.2
Number of Pages:	23
Page Range:	pp. 386-408
Identification Number:	10.1111/j.1574-6976.2007.00097.x
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Fondation pour la recherche médicale (FRM), Sixth Framework Programme (European Commission) (FP6)
Grant number:	DEQ200661107918 (FRM), LSHM-CT-2004-512138 (FP6)
URI:	http://wrap.warwick.ac.uk/id/eprint/30577

Data sourced from Thomson Reuters' Web of Knowledge

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