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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1499819
This article is part of the Research Topic Emerging Antimicrobials: Sources, Mechanisms of Action, Spectrum of Activity, Combination Antimicrobial Therapy, and Resistance Mechanisms View all 6 articles

Adenosine reverts tigecycline resistance in tet(X3)-carrying Escherichia coli

Provisionally accepted
Dongyang Ye Dongyang Ye *Jing Sun Jing Sun *Yiming Liu Yiming Liu *Jiashen Chang Jiashen Chang *Juan Wang Juan Wang *Zengqi Yang Zengqi Yang *
  • Northwest A&F University, Xianyang, China

The final, formatted version of the article will be published soon.

    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 damage, and cell membrane disruption in resistant bacteria. This study establishes a powerful metabolomics-driven strategy to potentiate antibiotic efficacy against drug-resistant pathogens. The adenosine-based adjuvant therapy represents a promising approach to combat the global crisis of antibiotic resistance.

    Keywords: Tet(X3), tigecycline, Adenosine, antimicrobial resistance, Metabolomics, metabolic reprogramming

    Received: 21 Sep 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Ye, Sun, Liu, Chang, Wang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dongyang Ye, Northwest A&F University, Xianyang, China
    Jing Sun, Northwest A&F University, Xianyang, China
    Yiming Liu, Northwest A&F University, Xianyang, China
    Jiashen Chang, Northwest A&F University, Xianyang, China
    Juan Wang, Northwest A&F University, Xianyang, China
    Zengqi Yang, Northwest A&F University, Xianyang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.