Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies

文献类型： 外文期刊

第一作者： Geng, Xiang

作者： Geng, Xiang;Li, Yuxi;Hao, Ruochen;Li, Zhun;Yang, Yajun;Liu, Xiwang;Li, Jianyong;Pu, Wanxia;Xu, Chunyan

作者机构：

关键词： Klebsiella pneumoniae; Antibiotic resistance; Isobavachalcone; Cell membrane; Biofilm

期刊名称：INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS （ 影响因子：4.6； 五年影响因子：5.0 ）

ISSN： 0924-8579

年卷期： 2024 年 64 卷 5 期

页码：

收录情况： SCI

摘要： Objective: Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae ( K. pneumoniae ) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo. Results: The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro c oncurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone. Conclusion: These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae -associated infections. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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