Factors essential for L,D-transpeptidase-mediated peptidoglycan cross-linking and β-lactam resistance in Escherichia coli.

Content Provider	Europe PMC
Author	Hugonnet, Jean-Emmanuel Mengin-Lecreulx, Dominique Monton, Alejandro den Blaauwen, Tanneke Carbonnelle, Etienne Veckerlé, Carole Brun, Yves, V. van Nieuwenhze, Michael Bouchier, Christiane Tu, Kuyek Rice, Louis B Arthur, Michel
Editor	Gilmore, Michael S
Abstract	The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in Escherichia coli more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance. Production of YcbB was therefore sufficient to switch the role of (p)ppGpp from antibiotic tolerance to high-level β-lactam resistance. This observation identifies a new mode of peptidoglycan polymerization in E. coli that relies on an unexpectedly small number of enzyme activities comprising the glycosyltransferase activity of class A PBP1b and the D,D-carboxypeptidase activity of DacA in addition to the L,D-transpeptidase activity of YcbB.DOI: http://dx.doi.org/10.7554/eLife.19469.001
Journal	eLife
Volume Number	5
PubMed Central reference number	PMC5089857
PubMed reference number	27767957
e-ISSN	2050084X
DOI	10.7554/elife.19469
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2016-10-21
Access Restriction	Open
Rights License	This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Subject Keyword	β-lactam PBP1b PBP5 L,D-transpeptidase mecillinam (p)ppGpp E. coli
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Neuroscience Medicine Biochemistry, Genetics and Molecular Biology