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Chem Commun (Camb). 2018 Sep 25;54(75):10630-10633. doi: 10.1039/c8cc05281f. Epub 2018 Sep 4.

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

Author information

1
School of Molecular Sciences, University of Western Australia, Crawley, WA 6009, Australia. keith.stubbs@uwa.edu.au.
2
Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T2N2, Canada. Brian.mark@umanitoba.ca.
3
School of Molecular Sciences, University of Western Australia, Crawley, WA 6009, Australia. keith.stubbs@uwa.edu.au and School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia.
4
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.

PMID:
30178799
DOI:
10.1039/c8cc05281f
[Indexed for MEDLINE]

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