Factors Essential for L,D-transpeptidase-mediated Peptidoglycan Cross-linking and β-lactam Resistance in

Overview

Journal Elife

Specialty Biology

Date 2016 Nov 2

PMID 27767957

Citations 86

Authors

Jean-Emmanuel Hugonnet

Dominique Mengin-Lecreulx

Alejandro Monton

Tanneke den Blaauwen

Etienne Carbonnelle

Carole Veckerle

Yves V Brun

Michael Van Nieuwenhze

Christiane Bouchier

Kuyek Tu

Louis B Rice

Michel Arthur

Affiliations

Soon will be listed here.

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 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 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.

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