Substrate Specificity of OXA-48 after β5-β6 Loop Replacement.


Journal

ACS infectious diseases
ISSN: 2373-8227
Titre abrégé: ACS Infect Dis
Pays: United States
ID NLM: 101654580

Informations de publication

Date de publication:
08 05 2020
Historique:
pubmed: 12 3 2020
medline: 17 6 2021
entrez: 12 3 2020
Statut: ppublish

Résumé

OXA-48 carbapenemase has rapidly spread in many countries worldwide with several OXA-48-variants being described, differing by a few amino acid (AA) substitutions or deletions, mostly in the β5-β6 loop. While single AA substitutions have only a minor impact on OXA-48 hydrolytic profiles, others with 4 AA deletions result in loss of carbapenem hydrolysis and gain of expanded-spectrum cephalosporin (ESC) hydrolysis. We have replaced the β5-β6 loop of OXA-48 with that of OXA-18, a clavulanic-acid inhibited oxacillinase capable of hydrolyzing ESCs but not carbapenems. The hybrid enzyme OXA-48Loop18 was able to hydrolyze ESCs and carbapenems (although with a lower

Identifiants

pubmed: 32156115
doi: 10.1021/acsinfecdis.9b00452
doi:

Substances chimiques

Carbapenems 0
Cephalosporins 0
beta-Lactamases EC 3.5.2.6

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1032-1043

Auteurs

Laura Dabos (L)

EA7361 "Structure, Dynamic, Function and Expression of Broad Spectrum β-Lactamases", Université Paris Sud, Université Paris Saclay, LabEx Lermit, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, France.
Evolution and Ecology of Resistance to Antibiotics Unit, Institut Pasteur-APHP-Université Paris Sud, 75015 Paris, France.

Agustin Zavala (A)

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, Labex LERMIT, 91190 Gif-sur-Yvette, France.

Rémy A Bonnin (RA)

EA7361 "Structure, Dynamic, Function and Expression of Broad Spectrum β-Lactamases", Université Paris Sud, Université Paris Saclay, LabEx Lermit, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, France.
Evolution and Ecology of Resistance to Antibiotics Unit, Institut Pasteur-APHP-Université Paris Sud, 75015 Paris, France.
Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriaceae, 94270 Le Kremlin-Bicêtre, France.

Oliver Beckstein (O)

Department of Physics and Center for Biological Physics, Arizona State University, Tempe, 85281 Arizona, United States.

Pascal Retailleau (P)

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, Labex LERMIT, 91190 Gif-sur-Yvette, France.

Bogdan I Iorga (BI)

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, Labex LERMIT, 91190 Gif-sur-Yvette, France.

Thierry Naas (T)

EA7361 "Structure, Dynamic, Function and Expression of Broad Spectrum β-Lactamases", Université Paris Sud, Université Paris Saclay, LabEx Lermit, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, France.
Evolution and Ecology of Resistance to Antibiotics Unit, Institut Pasteur-APHP-Université Paris Sud, 75015 Paris, France.
Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriaceae, 94270 Le Kremlin-Bicêtre, France.
Bacteriology-Hygiene Unit, Assistance Publique/Hôpitaux de Paris, Bicêtre Hospital, 94270 Le Kremlin-Bicêtre, France.

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Classifications MeSH