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. 2014 Nov;58(11):6536-43.
doi: 10.1128/AAC.03238-14. Epub 2014 Aug 18.

Distinct roles of major peptidoglycan recycling enzymes in β-Lactamase production in Shewanella oneidensis

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Distinct roles of major peptidoglycan recycling enzymes in β-Lactamase production in Shewanella oneidensis

Jianhua Yin et al. Antimicrob Agents Chemother. 2014 Nov.

Abstract

β-Lactam antibiotics were the earliest discovered and are the most widely used group of antibiotics that work by inactivating penicillin-binding proteins to inhibit peptidoglycan biosynthesis. As one of the most efficient defense strategies, many bacteria produce β-lactam-degrading enzymes, β-lactamases, whose biochemical functions and regulation have been extensively studied. A signal transduction pathway for β-lactamase induction by β-lactam antibiotics, consisting of the major peptidoglycan recycling enzymes and the LysR-type transcriptional regulator, AmpR, has been recently unveiled in some bacteria. Because inactivation of some of these proteins, especially the permease AmpG and the β-hexosaminidase NagZ, results in substantially elevated susceptibility to the antibiotics, these have been recognized as potential therapeutic targets. Here, we show a contrasting scenario in Shewanella oneidensis, in which the homologue of AmpR is absent. Loss of AmpG or NagZ enhances β-lactam resistance drastically, whereas other identified major peptidoglycan recycling enzymes are dispensable. Moreover, our data indicate that there exists a parallel signal transduction pathway for β-lactamase induction, which is independent of either AmpG or NagZ.

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Figures

FIG 1
FIG 1
Improved ampicillin resistance in nagZ and ampG mutants is dependent on the expression of BlaA. PblaA promoter activities were determined by measuring β-galactosidase (in Miller units) using the PblaA-lacZ reporter system in ΔampD, ΔampE, ΔnagZ, ΔampG, and ΔampDΔnagZ strains in the absence and presence of ampicillin at 50 μg/ml and 2.5 μg/ml. Results are averages from at least three replicates, and the error bars represent standard deviations (SD). WT, wild type.

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