Pyruvate Abundance Confounds Aminoglycoside Killing of Multidrug-Resistant Bacteria via Glutathione Metabolism.

ABSTRACT: To explore whether the metabolic state reprogramming approach may be used to explore previously unknown metabolic pathways that contribute to antibiotic resistance, especially those that have been neglected in previous studies, pyruvate reprogramming was performed to reverse the resistance of multidrug-resistant Edwardsiella tarda. Surprisingly, we identified a pyruvate-regulated glutathione system that occurs by boosting glycine, serine, and threonine metabolism. Moreover, cysteine and methionine metabolism played a key role in this reversal. This process involved pyruvate-depressed glutathione and pyruvate-promoted glutathione oxidation, which was attributed to the elevated glutathione peroxidase and depressed glutathione reductase that was inhibited by glycine. This regulation in

SUBMITTER: Xiang J 

PROVIDER: S-EPMC11654824 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature