Issue 75, 2018
From the journal:

Chemical Communications

A mechanism-based GlcNAc-inspired cyclophellitol inactivator of the peptidoglycan recycling enzyme NagZ reverses resistance to β-lactams in Pseudomonas aeruginosa†

Louisa A. Ho,a   Judith L. Winogrodzki,b   Aleksandra W. Debowski, ORCID logo ac   Zarina Madden,d   David J. Vocadlo, ORCID logo d   Brian L. Mark ORCID logo *b  and  Keith A. Stubbs ORCID logo *a  

* Corresponding authors

a School of Molecular Sciences, University of Western Australia, Crawley, WA 6009, Australia
E-mail: keith.stubbs@uwa.edu.au

b Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
E-mail: Brian.mark@umanitoba.ca

c School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia

d Department of Chemistry, Simon Fraser University, Burnaby, BC V5A1S6, Canada

Abstract

The development of a potent mechanism-based inactivator of NagZ, an enzyme critical to the production of inducible AmpC β-lactamase in Gram-negative bacteria, is presented. This inactivator significantly reduces MIC values for important β-lactams against a clinically relevant strain of Pseudomonas aeruginosa.

Graphical abstract: A mechanism-based GlcNAc-inspired cyclophellitol inactivator of the peptidoglycan recycling enzyme NagZ reverses resistance to β-lactams in Pseudomonas aeruginosa

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Article information

DOI
https://doi.org/10.1039/C8CC05281F
Article type
Communication
Submitted
01 Jul 2018
Accepted
24 Aug 2018
First published
27 Aug 2018

Chem. Commun., 2018,54, 10630-10633

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A mechanism-based GlcNAc-inspired cyclophellitol inactivator of the peptidoglycan recycling enzyme NagZ reverses resistance to β-lactams in Pseudomonas aeruginosa

L. A. Ho, J. L. Winogrodzki, A. W. Debowski, Z. Madden, D. J. Vocadlo, B. L. Mark and K. A. Stubbs, Chem. Commun., 2018, 54, 10630 DOI: 10.1039/C8CC05281F

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