ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens


Journal

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061

Informations de publication

Date de publication:
21 05 2020
Historique:
received: 03 12 2019
accepted: 05 03 2020
pubmed: 18 3 2020
medline: 22 6 2021
entrez: 18 3 2020
Statut: epublish

Résumé

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and

Identifiants

pubmed: 32179522
pii: AAC.02415-19
doi: 10.1128/AAC.02415-19
pmc: PMC7269481
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Carbapenems 0
beta-Lactamase Inhibitors 0
beta-Lactamases EC 3.5.2.6
Meropenem FV9J3JU8B1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020 Samuelsen et al.

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Auteurs

Ørjan Samuelsen (Ø)

Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway orjan.samuelsen@unn.no pal.rongved@farmasi.uio.no.
Department of Pharmacy, UiT The Arctic University of Norway, Tromsø, Norway.

Ove Alexander Høgmoen Åstrand (OAH)

Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway.

Christopher Fröhlich (C)

Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway.

Adam Heikal (A)

Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.

Susann Skagseth (S)

The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway.

Trine Josefine Olsen Carlsen (TJO)

The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway.

Hanna-Kirsti S Leiros (HS)

The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway.

Annette Bayer (A)

Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway.

Christian Schnaars (C)

Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway.

Geir Kildahl-Andersen (G)

Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway.

Silje Lauksund (S)

Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
Department of Pharmacy, UiT The Arctic University of Norway, Tromsø, Norway.

Sarah Finke (S)

Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.

Sandra Huber (S)

Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway, Tromsø, Norway.

Tor Gjøen (T)

Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.

Adriana Magalhaes Santos Andresen (AMS)

Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.

Ole Andreas Økstad (OA)

Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.

Pål Rongved (P)

Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway orjan.samuelsen@unn.no pal.rongved@farmasi.uio.no.

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Classifications MeSH