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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1426603
This article is part of the Research Topic New Therapeutic Strategies Against Carbapenem-Resistant Gram-negative Bacteria View all 12 articles

Ginkgolic Acid as a carbapenem synergist against KPC-2 positive Klebsiella pneumoniae

Provisionally accepted
Yuping Song Yuping Song 1*Yinuo Zou Yinuo Zou 2*Lei Xu Lei Xu 2*Jianfeng Wang Jianfeng Wang 2Xuming Deng Xuming Deng 2Yonglin Zhou Yonglin Zhou 3*Dan Li Dan Li 1*
  • 1 First Affiliated Hospital of Jilin University, Changchun, China
  • 2 Jilin University, Changchun, Hebei Province, China
  • 3 Ningxia University, Yinchuan, Ningxia Hui Region, China

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

    The successful evolution of KPC in bacteria restricted the clinical practice of carbapenems. This dilemma deteriorated the prognosis of associated infections and hence attracted increasing attention from researchers to explore alternative therapeutic options. Here, we found that Ginkgolic Acid (C13:0) (GA) exhibited effective KPC-2 inhibitory activity, both in laboratory strain and clinical strain containing KPC-2. Its synergistic effect with carbapenems against KPC-2 positive Klebsiella pneumoniae (K. pneumoniae) was subsequently confirmed by checkboard minimum inhibitory concentration (MIC) assay, time-killing assay, disk diffusion method and live/dead bacteria staining analysis. Further explorations revealed that GA could competitively bind to the active pocket of KPC-2 with meropenem (MEM) via residues Trp104, Gly235 and Leu166. The secondary structure and functional groups of KPC-2 were subsequently altered, which may be the main mechanism by which GA exerted its KPC-2 activity inhibitory effect. In addition, GA was also found to synergise with MEM to disrupt membrane integrity and increase membrane permeability, which may be another mechanism by which GA reinforces the bactericidal ability of carbapenems. Our study indicated that GA was an excellent KPC-2 inhibitor which could prolong the lifespan of carbapenems and improve the prognosis of patients.

    Keywords: KPC-2, Ginkgolic acid (C13:0), Carbapenems, Klebsiella pneumoniae, Resistance

    Received: 01 May 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Song, Zou, Xu, Wang, Deng, Zhou and Li. 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:
    Yuping Song, First Affiliated Hospital of Jilin University, Changchun, China
    Yinuo Zou, Jilin University, Changchun, 130012, Hebei Province, China
    Lei Xu, Jilin University, Changchun, 130012, Hebei Province, China
    Yonglin Zhou, Ningxia University, Yinchuan, 750021, Ningxia Hui Region, China
    Dan Li, First Affiliated Hospital of Jilin University, Changchun, China

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