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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1458945
This article is part of the Research Topic Emerging Leaders in Antibiotic Resistance: Pioneering Research and Future Directions View all 7 articles

Disruption of Zinc Homeostasis Reverses Tigecycline Resistance in Klebsiella Pneumoniae

Provisionally accepted
Jinyu Wang Jinyu Wang Cuiping Xia Cuiping Xia Zhaoxin Xia Zhaoxin Xia Jilu Shen Jilu Shen *
  • First Affiliated Hospital of Anhui Medical University, Hefei, China

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

    The antimicrobial potency of zinc is attributed to its capacity to compromise bacterial structure and protein functionality, thereby achieving the inhibition and eradication of bacteria. However, despite its antimicrobial prowess, bacteria have developed a variety of mechanisms to expel excess zinc ions from their cells. This evolutionary advancement has allowed numerous bacteria to thrive in environments rich in metal ions at high concentrations, thereby circumscribing the clinical application of metal ions as antimicrobial agents.In this study, we employed the zinc ionophore PBT2 to elevate intracellular zinc ion levels in Klebsiella pneumoniae and discovered that PBT2 reversed the resistance of Klebsiella pneumoniae to tigecycline. Our research indicates that PBT2 can increase the concentration of intracellular zinc ions in K. pneumoniae, suppress the activity of superoxide dismutase within the cell, and elevate the concentration of reactive oxygen species within the bacterial cell, thus impairing the oxidative stress response. Concurrently, the disruption of zinc homeostasis significantly inhibits the cell wall synthesis pathway in Klebsiella pneumoniae, potentially restricting the efflux pump mechanism that predominantly drives tigecycline resistance to some extent. This discovery paves the way for innovative strategies and approaches in the clinical development of novel antimicrobial agents in the future.

    Keywords: PBT2, Zinc, GlmU, tigecycline, Klebsiella pneuminiae

    Received: 03 Jul 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Wang, Xia, Xia and Shen. 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: Jilu Shen, First Affiliated Hospital of Anhui Medical University, Hefei, China

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