Oxidized glutathione reverts carbapenem resistance in blaNDM-1-carrying Escherichia coli.
EMBO Mol Med
; 16(5): 1051-1062, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38565805
ABSTRACT
The emergence of drug-resistant Enterobacteriaceae carrying plasmid-mediated ß-lactamase genes has become a significant threat to public health. Organisms in the Enterobacteriaceae family containing New Delhi metallo-ß-lactamase1 (NDM-1) and its variants, which are capable of hydrolyzing nearly all ß-lactam antibacterial agents, including carbapenems, are referred to as superbugs and distributed worldwide. Despite efforts over the past decade, the discovery of an NDM-1 inhibitor that can reach the clinic remains a challenge. Here, we identified oxidized glutathione (GSSG) as a metabolic biomarker for blaNDM-1 using a non-targeted metabolomics approach and demonstrated that GSSG supplementation could restore carbapenem susceptibility in Escherichia coli carrying blaNDM-1 in vitro and in vivo. We showed that exogenous GSSG promotes the bactericidal effects of carbapenems by interfering with intracellular redox homeostasis and inhibiting the expression of NDM-1 in drug-resistant E. coli. This study establishes a metabolomics-based strategy to potentiate metabolism-dependent antibiotic efficacy for the treatment of antibiotic-resistant bacteria.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Beta-Lactamases
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Carbapenêmicos
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Escherichia coli
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Glutationa
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Antibacterianos
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO Mol Med
Ano de publicação:
2024
Tipo de documento:
Article