Penicillanic Acid Sulfones Inactivate the Extended-Spectrum β-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of β-Lactamase Inhibition.


Journal

mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231

Informations de publication

Date de publication:
28 06 2022
Historique:
pubmed: 26 5 2022
medline: 1 7 2022
entrez: 25 5 2022
Statut: ppublish

Résumé

β-Lactamases hydrolyze β-lactam antibiotics and are major determinants of antibiotic resistance in Gram-negative pathogens. Enmetazobactam (formerly AAI101) and tazobactam are penicillanic acid sulfone (PAS) β-lactamase inhibitors that differ by an additional methyl group on the triazole ring of enmetazobactam, rendering it zwitterionic. In this study, ultrahigh-resolution X-ray crystal structures and mass spectrometry revealed the mechanism of PAS inhibition of CTX-M-15, an extended-spectrum β-lactamase (ESBL) globally disseminated among

Identifiants

pubmed: 35612361
doi: 10.1128/mbio.01793-21
pmc: PMC9239225
doi:

Substances chimiques

Anti-Bacterial Agents 0
beta-Lactamase Inhibitors 0
Serine 452VLY9402
beta-lactamase CTX-M-15 EC 3.5.2.-
beta-Lactamases EC 3.5.2.6
Lysine K3Z4F929H6
Sulbactam S4TF6I2330
Tazobactam SE10G96M8W

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0179321

Subventions

Organisme : NIH HHS
ID : S10 OD026882
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI072219
Pays : United States
Organisme : BLRD VA
ID : I01 BX001974
Pays : United States
Organisme : Medical Research Council
ID : MR/T016035/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014400/1
Pays : United Kingdom
Organisme : BLRD VA
ID : I01 BX002872
Pays : United States

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Auteurs

Philip Hinchliffe (P)

School of Cellular and Molecular Medicine, University of Bristolgrid.5337.2, Bristol, United Kingdom.

Catherine L Tooke (CL)

School of Cellular and Molecular Medicine, University of Bristolgrid.5337.2, Bristol, United Kingdom.

Christopher R Bethel (CR)

Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, Ohio, USA.

Benlian Wang (B)

Department of Proteomics and Bioinformatics, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.

Christopher Arthur (C)

School of Chemistry, University of Bristolgrid.5337.2, Bristol, United Kingdom.

Kate J Heesom (KJ)

Proteomics Facility, Faculty of Life Sciences, University of Bristolgrid.5337.2, Bristol, United Kingdom.

Stuart Shapiro (S)

Allecra Therapeutics SAS, Saint-Louis, France.

Daniela M Schlatzer (DM)

Department of Proteomics and Bioinformatics, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.

Krisztina M Papp-Wallace (KM)

Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, Ohio, USA.
Department of Medicine, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.
Department of Biochemistry, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.

Robert A Bonomo (RA)

Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, Ohio, USA.
Department of Medicine, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.
Department of Biochemistry, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.
Department of Pharmacology, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.
Department of Molecular Biology and Microbiology, Case Western Reserve Universitygrid.67105.35 School of Medicine, Cleveland, Ohio, USA.
CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA.

James Spencer (J)

School of Cellular and Molecular Medicine, University of Bristolgrid.5337.2, Bristol, United Kingdom.

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Classifications MeSH