Modulation of the Specificity of Carbapenems and Diazabicyclooctanes for Selective Activity against Mycobacterium tuberculosis.
Mycobacterium tuberculosis
carbapenem
carbapenemase
diazabicyclooctane
narrow-spectrum drug
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:
20 09 2022
20 09 2022
Historique:
pubmed:
10
8
2022
medline:
24
9
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
Treatment of multidrug-resistant tuberculosis with combinations of carbapenems and β-lactamase inhibitors carries risks for dysbiosis and for the development of resistances in the intestinal microbiota. Using Escherichia coli producing carbapenemase KPC-2 as a model, we show that carbapenems can be modified to obtain drugs that are inactive against E. coli but retain antitubercular activity. Furthermore, functionalization of the diazabicyclooctanes scaffold provided drugs that did not effectively inactivate KPC-2 but retained activity against Mycobacterium tuberculosis targets.
Identifiants
pubmed: 35943263
doi: 10.1128/aac.02357-21
pmc: PMC9487530
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
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
Pagination
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