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.
AAI101
CTX-M-15
antibiotic resistance
enmetazobactam
extended-spectrum β-lactamase
inhibitor
lysinoalanine
tazobactam
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
28 06 2022
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
e0179321Subventions
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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