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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2025-02-01
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| author | Youqi Ji Yinhuan Wang Zhangkai Xu Danlei Chen Zhendi Yu Qingyi Shao Xin Hong Zishu Liu Dongqing Cheng |
| author_facet | Youqi Ji Yinhuan Wang Zhangkai Xu Danlei Chen Zhendi Yu Qingyi Shao Xin Hong Zishu Liu Dongqing Cheng |
| author_sort | Youqi Ji |
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| description | 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. |
| format | Article |
| id | doaj-art-72b7e51e2b284a3ca70674de526a8d4d |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-72b7e51e2b284a3ca70674de526a8d4d2025-08-20T02:12:31ZengMDPI AGMolecules1420-30492025-02-0130366310.3390/molecules30030663Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i>Youqi Ji0Yinhuan Wang1Zhangkai Xu2Danlei Chen3Zhendi Yu4Qingyi Shao5Xin Hong6Zishu Liu7Dongqing Cheng8School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaZhejiang Institute for Food and Drug Control, Hangzhou 310052, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaDepartment of Green Pharmaceutical Collaborative Innovation Center, School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaBackground: 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.https://www.mdpi.com/1420-3049/30/3/663<i>Iris tectorum</i><i>Escherichia coli</i>β-lactam resistancehistidine kinasephosphorylationmolecular docking |
| spellingShingle | Youqi Ji Yinhuan Wang Zhangkai Xu Danlei Chen Zhendi Yu Qingyi Shao Xin Hong Zishu Liu Dongqing Cheng Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> Molecules <i>Iris tectorum</i> <i>Escherichia coli</i> β-lactam resistance histidine kinase phosphorylation molecular docking |
| title | Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> |
| title_full | Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> |
| title_fullStr | Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> |
| title_full_unstemmed | Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> |
| title_short | Small Molecules from Medicinal Plant <i>Iris tectorum</i> as Histidine Kinase Inhibitor to Resensitize β-Lactam-Resistant <i>Escherichia coli</i> |
| title_sort | small molecules from medicinal plant i iris tectorum i as histidine kinase inhibitor to resensitize β lactam resistant i escherichia coli i |
| topic | <i>Iris tectorum</i> <i>Escherichia coli</i> β-lactam resistance histidine kinase phosphorylation molecular docking |
| url | https://www.mdpi.com/1420-3049/30/3/663 |
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