Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i>

Background: Due to the widespread use of broad-spectrum antibiotics, the problem of antibiotic resistance has become an increasingly serious global threat. One of the key mechanisms of <i>Escherichia coli</i> resistance to beta-lactam antibiotics is the production of beta-lactamase enzym...

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Main Authors: Youqi Ji, Yinhuan Wang, Zhangkai Xu, Danlei Chen, Zhendi Yu, Qingyi Shao, Xin Hong, Zishu Liu, Dongqing Cheng
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/3/663
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Summary:Background: Due to the widespread use of broad-spectrum antibiotics, the problem of antibiotic resistance has become an increasingly serious global threat. One of the key mechanisms of <i>Escherichia coli</i> resistance to beta-lactam antibiotics is the production of beta-lactamase enzymes, which poses a dilemma for clinicians in selecting antibiotics when faced with resistant bacterial infections. However, research on the reversal of bacterial resistance is limited. Methods: This study involved the preparation of <i>Iris tectorum</i> extract and detection of its effects on antibiotics sensitivity, extended-spectrum beta-lactamase (ESBL) gene expression, and histidine kinase phosphorylation levels in β-lactam antibiotic-resistant <i>Escherichia coli</i>. Additionally, analyses of the active ingredients of <i>Iris tectorum</i> extract were conducted with a liquid chromatography–mass spectrometer, and the binding sites were predicted by molecular docking. Results: <i>Iris tectorum</i> extract could restore the sensitivity of <i>Escherichia coli</i> to beta-lactam antibiotics and reduce the expression levels of ESBL genes and histidine phosphorylation levels. The active ingredients of <i>Iris tectorum</i> extract may be irigenin and tectorigenin, and these two small molecules could bind to histidine kinase to inhibit phosphorylation. Conclusions: <i>Iris tectorum</i> extract may serve as an antibiotic adjuvant, restoring the sensitivity of antibiotic-resistant bacteria by inhibiting histidine kinase phosphorylation, thereby alleviating the problem of <i>Escherichia coli</i> resistance to β-lactam antibiotics.
ISSN:1420-3049