Exogenous adenosine counteracts tigecycline resistance in <i>tet</i>(X3)-harboring <i>Escherichia coli</i>.

ABSTRACT: The rapid spread of antibiotic resistance poses a global health crisis. Tigecycline is a last-resort antibiotic, but the recent emergence of the plasmid-borne tet(X3) gene conferring high-level tigecycline resistance is deeply concerning. Here, we report a metabolomics-guided approach to overcome tet(X3)-mediated resistance. Using untargeted metabolomics, we identified adenosine as a key metabolic biomarker associated with tet(X3) expression. Remarkably, supplementation with exogenous adenosine was able to restore tigecycline susceptibility in tet(X3)-positive Escherichia coli both in vitro and in vivo. Our mechanistic investigations reveal that adenosine enhances the bactericidal effects of tigecycline by inducing oxidative stress, DNA/RNA

SUBMITTER: Sun J 

PROVIDER: S-EPMC12323663 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature